CFHR4 complement factor H related 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CFHR4provided by HGNC
Official Full Name: complement factor H related 4provided by HGNC
Primary source: HGNC:HGNC:16979
See related: Ensembl:ENSG00000134365 MIM:605337; AllianceGenome:HGNC:16979
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FHR4; CFHL4; FHR-4
Summary: This gene is a member of the complement factor H (CFH) gene family, and encodes one of the 5 CFH-related (CFHR) proteins. These 5 genes are closely linked to the CFH gene on chromosome 1q31-q32. The CFHRs are secreted plasma proteins synthesized primarily by the hepatocytes, and composed of highly-related short consensus repeats (SCRs). This protein enhances the cofactor activity of CFH, and is involved in complement regulation. It can associate with lipoproteins and may play a role in lipid metabolism. Alternatively spliced transcript variants encoding different isoforms (varying in the number of SCRs) have been described for this gene. [provided by RefSeq, Jan 2011]
Expression: Restricted expression toward liver (RPKM 22.1) See more
Orthologs: all
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Genomic context

Location:: 1q31.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (196888052..196918633)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (196149839..196180430)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (196857182..196887763)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.
Title: Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.
CFH and CFHR structural variants in atypical Hemolytic Uremic Syndrome: Prevalence, genomic characterization and impact on outcome.
Title: CFH and CFHR structural variants in atypical Hemolytic Uremic Syndrome: Prevalence, genomic characterization and impact on outcome.
Identification of CFHR4 as a Potential Prognosis Biomarker Associated With lmmune Infiltrates in Hepatocellular Carcinoma.
Title: Identification of CFHR4 as a Potential Prognosis Biomarker Associated With lmmune Infiltrates in Hepatocellular Carcinoma.
FHR-4 as a key molecular player contributing to complement dysregulation in the age-related macular degeneration.FHR-4 is expressed in the liver but not in the eye.
Title: Increased circulating levels of Factor H-Related Protein 4 are strongly associated with age-related macular degeneration.
The SNP rs3753396 in CFH and SNP rs6685931 in CFHR4 are associated with systemic complement activation levels. The SNP rs6685931 in CFHR4 and its linked haplotype H1-2 also conferred a risk for age-related macular degeneration (AMD) development, and therefore could be used to identify AMD patients who would benefit most from complement-inhibiting therapies.
Title: Genome-Wide Association Study Reveals Variants in CFH and CFHR4 Associated with Systemic Complement Activation: Implications in Age-Related Macular Degeneration.
Reports an association between a rare variant in the complement factor H-related 4 (CFHR4) gene and phenytoin-induced maculopapular exanthema in Europeans. This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity.
Title: Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients.
The combination of three proteins - apolipoprotein A-IV, complement factor H-related protein 4 and platelet basic protein - demonstrated the best classification performance for our data for diagnosis of growth hormone defic.
Title: Identification of candidate serum biomarkers of childhood-onset growth hormone deficiency using SWATH-MS and feature selection.
Next-generation sequencing of the CFH region identified putatively functional variants (missense, splice site and indel) on the four common haplotypes. We found no expression of any of the five CFH-related genes in the retina or RPE/Choroid/Sclera, in contrast to the liver, which is the main source of the circulating proteins. [CFHR4]
Title: Sequence and Expression of Complement Factor H Gene Cluster Variants and Their Roles in Age-Related Macular Degeneration Risk.
Studies indicate that complement factor H-related proteins (FHR1-5) may enhance complement activation, with important implications for the role of these proteins in disease.
Title: Factor H-related proteins determine complement-activating surfaces.
Factor H-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with C3b protein
Title: Factor H-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with C3b protein.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Atypical hemolytic-uremic syndrome MedGen: C2931788 GeneReviews: Genetic Atypical Hemolytic-Uremic Syndrome	Compare labs

EBI GWAS Catalog

Description
Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies susceptibility loci for IgA nephropathy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Ischemic stroke is associated with the ABO locus: the EuroCLOT study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-76077 (e-PCR)
- UniSTS:4616

NoName (e-PCR)
- UniSTS:482090

SHGC-76076 (e-PCR)
- UniSTS:64156

NoName (e-PCR)
- UniSTS:491189

NoName (e-PCR)
- UniSTS:480509

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables complement component C3b binding	IBA Inferred from Biological aspect of Ancestor more info
enables lipid transporter activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in complement activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in lipid transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: complement factor H-related protein 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_028159.1 RefSeqGene

Range

5039..35620

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GenBank, FASTA, Sequence Viewer (Graphics), LRG_1224

mRNA and Protein(s)

NM_001201550.3 → NP_001188479.1 complement factor H-related protein 4 isoform 1 precursor

See identical proteins and their annotated locations for NP_001188479.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1, also known as FHR-4A).

Source sequence(s)

AJ640130, AK292752, BX248415, X98337

Consensus CDS

CCDS91133.1

UniProtKB/Swiss-Prot

A8K9N7, B1ALQ9, C9J7J7, Q5DVJ7, Q92496, Q9UJY6

Related

ENSP00000477162.2, ENST00000608469.6

Conserved Domains (3) summary

cd00033
Location:458 → 513

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

PHA02927
Location:339 → 577

PHA02927; secreted complement-binding protein; Provisional

pfam00084
Location:27 → 83

Sushi; Sushi repeat (SCR repeat)
NM_001201551.2 → NP_001188480.1 complement factor H-related protein 4 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate acceptor splice site in the 5' coding region compared to variant 1, resulting in an isoform (2) shorter by 1 aa compared to isoform 1.

Source sequence(s)

AJ640130, AK292752, BX248415

Consensus CDS

CCDS55671.1

UniProtKB/Swiss-Prot

Q92496

Related

ENSP00000356386.2, ENST00000367416.6

Conserved Domains (3) summary

cd00033
Location:457 → 512

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

PHA02927
Location:338 → 576

PHA02927; secreted complement-binding protein; Provisional

pfam00084
Location:26 → 82

Sushi; Sushi repeat (SCR repeat)
NM_006684.5 → NP_006675.2 complement factor H-related protein 4 isoform 3 precursor

See identical proteins and their annotated locations for NP_006675.2

Status: REVIEWED

Description

Transcript Variant: This variant (3) is missing four consecutive coding exons compared to variant 1. However, it maintains the reading frame and encodes isoform 3 (also known as FHR-4B), which is shorter but has the same N- and C-termini compared to isoform 1.

Source sequence(s)

AJ640130, AK292752, X98337

Consensus CDS

CCDS41451.1

UniProtKB/Swiss-Prot

Q92496

Related

ENSP00000251424.4, ENST00000251424.8

Conserved Domains (3) summary

cd00033
Location:211 → 266

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

PHA02927
Location:92 → 330

PHA02927; secreted complement-binding protein; Provisional

pfam00084
Location:27 → 83

Sushi; Sushi repeat (SCR repeat)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

196888052..196918633

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047440640.1 → XP_047296596.1 complement factor H-related protein 4 isoform X2
XM_047440639.1 → XP_047296595.1 complement factor H-related protein 4 isoform X1

Related

ENST00000699463.1
XM_017000111.2 → XP_016855600.1 complement factor H-related protein 4 isoform X3
XM_017000113.2 → XP_016855602.1 complement factor H-related protein 4 isoform X5
XM_047440659.1 → XP_047296615.1 complement factor H-related protein 4 isoform X4
XM_047440683.1 → XP_047296639.1 complement factor H-related protein 4 isoform X6

Reference GRCh38.p14 PATCHES

Genomic

NW_025791754.1 Reference GRCh38.p14 PATCHES

Range

653141..683733

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054332739.1 → XP_054188714.1 complement factor H-related protein 4 isoform X7
XM_054332735.1 → XP_054188710.1 complement factor H-related protein 4 isoform X2
XM_054332734.1 → XP_054188709.1 complement factor H-related protein 4 isoform X1
XM_054332736.1 → XP_054188711.1 complement factor H-related protein 4 isoform X3
XM_054332738.1 → XP_054188713.1 complement factor H-related protein 4 isoform X5
XM_054332737.1 → XP_054188712.1 complement factor H-related protein 4 isoform X4
XM_054332740.1 → XP_054188715.1 complement factor H-related protein 4 isoform X6

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

196149839..196180430

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054333945.1 → XP_054189920.1 complement factor H-related protein 4 isoform X8
XM_054333942.1 → XP_054189917.1 complement factor H-related protein 4 isoform X2
XM_054333941.1 → XP_054189916.1 complement factor H-related protein 4 isoform X1
XM_054333943.1 → XP_054189918.1 complement factor H-related protein 4 isoform X3
XM_054333944.1 → XP_054189919.1 complement factor H-related protein 4 isoform X4
XM_054333946.1 → XP_054189921.1 complement factor H-related protein 4 isoform X6