SLC44A4 solute carrier family 44 member 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC44A4provided by HGNC
Official Full Name: solute carrier family 44 member 4provided by HGNC
Primary source: HGNC:HGNC:13941
See related: Ensembl:ENSG00000204385 MIM:606107; AllianceGenome:HGNC:13941
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: CTL4; NG22; TPPT; DFNA72; hTPPT1; C6orf29
Summary: The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]
Expression: Biased expression in colon (RPKM 98.7), stomach (RPKM 72.4) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.33

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (31863192..31878997, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (31716432..31732232, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (31830969..31846774, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology.
Title: Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology.
We found that rs2736428 was significantly associated with UC risk (allelic p = 0.0004), and the CT and TT genotypes of rs2736428 had a higher distribution compared with the CC genotypes (genotypic p = 0.001), suggesting that the T allele was a risk allele (odds ratio = 1.45, 95% confidence interval = 1.18-1.78). Moreover, one haplotype block that included rs2736428 was found to be strongly associated with UC risk as well
Title: Evaluating the Association of Common Variants of the SLC44A4 Gene with Ulcerative Colitis Susceptibility in the Han Chinese Population.
Whole-exome sequencing revealed SLC44A4, which encodes the choline transport protein, as the pathogenic gene in this family. In the zebrafish model, downregulation of slc44a4 using morpholinos led to significant abnormalities in the zebrafish inner ear and lateral line neuromasts and contributed, to some extent, to disabilities in hearing and balance.
Title: SLC44A4 mutation causes autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss.
These results suggest (i) apparent allelic heterogeneity in CFB and genetic heterogeneity in SLC44A4 across different ethnic groups; (ii) shared ulcerative colitis genetic etiological factors among Asians
Title: A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility.
Critical genetic polymorphisms in SLC44A4, an ulcerative colitis susceptibility gene, have been identified in a genetic association study in North Indians.
Title: Identification of critical variants within SLC44A4, an ulcerative colitis susceptibility gene identified in a GWAS in north Indians.
epigenetic mechanisms (histone modifications) play a role in determining the tissue-specific pattern of expression of the TPPT along the GI tract.
Title: Mechanism(S) Involved in the Colon-Specific Expression of the Thiamine Pyrophosphate (Tpp) Transporter.
The results also provide an indirect support for a membrane topology for hTPPT with 10 transmembrane domains as predicted by the TMHMM transmembrane helixes prediction program.
Title: The human colonic thiamine pyrophosphate transporter (hTPPT) is a glycoprotein and N-linked glycosylation is important for its function.
Characterization of the SLC44A4 promoter and report the importance of both ELF3 and CREB-1 transcription factors in the maintenance of basal promoter activity in colonic epithelial cells.
Title: Regulation of basal promoter activity of the human thiamine pyrophosphate transporter SLC44A4 in human intestinal epithelial cells.
Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter.
Title: Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter.
These results indicate that CTL4 mediates ACh synthesis in non-neuronal cell lines and presents a mechanism to target non-neuronal ACh synthesis without affecting neuronal ACh synthesis.
Title: Choline transporter-like protein 4 (CTL4) links to non-neuronal acetylcholine synthesis.

Submit: New GeneRIF Correction See all GeneRIFs (13)

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
Hearing loss, autosomal dominant 72 MedGen: C4539886 OMIM: 617606 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association scan in north Indians reveals three novel HLA-independent risk loci for ulcerative colitis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci at chromosomes 13, 19 and 20 influence age at natural menopause. 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

RH46780 (e-PCR)
- UniSTS:22049

WI-19170 (e-PCR)
- UniSTS:22050

D8S2279 (e-PCR)
- UniSTS:473907

NoName (e-PCR)
- UniSTS:237636

D15S948E (e-PCR)
- UniSTS:153949

D15S1477 (e-PCR)
- UniSTS:474482

MN6S1424 (e-PCR)
- UniSTS:480405

D6S2052 (e-PCR)
- UniSTS:37014

STS-X69838 (e-PCR)
- UniSTS:23983

D6S2924 (e-PCR)
- UniSTS:464309

ksks210 (e-PCR)
- UniSTS:514243

MARC_12895-12896:999881472:3 (e-PCR)
- UniSTS:267471

RH70238 (e-PCR)
- UniSTS:16894

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables antiporter activity	IEA Inferred from Electronic Annotation more info
enables choline transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables choline transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables choline transmembrane transporter activity	TAS Traceable Author Statement more info
enables thiamine pyrophosphate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables thiamine pyrophosphate transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in acetylcholine biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in acetylcholine secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in choline transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in choline transport	IDA Inferred from Direct Assay more info	PubMed
involved_in choline transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuromast hair cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in otolith formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in phosphatidylcholine biosynthetic process	TAS Traceable Author Statement more info
involved_in positive regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in thiamine pyrophosphate transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in thiamine pyrophosphate transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in thiamine pyrophosphate transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transmembrane transport	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: choline transporter-like protein 4

Names: testicular tissue protein Li 48; thiamine pyrophosphate transporter 1

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_023058.1 RefSeqGene

Range

5050..20855

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001178044.2 → NP_001171515.1 choline transporter-like protein 4 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AI956094, AK300550, AK301596, BC014659

Consensus CDS

CCDS54990.1

UniProtKB/TrEMBL

A0A0G2JL76, A0A1U9X8K1

Related

ENSP00000364712.4, ENST00000375562.8

Conserved Domains (1) summary

pfam04515
Location:271 → 632

Choline_transpo; Plasma-membrane choline transporter
NM_001178045.2 → NP_001171516.1 choline transporter-like protein 4 isoform 3

See identical proteins and their annotated locations for NP_001171516.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AI956094, AK300550, BC014659, DC392935

Consensus CDS

CCDS54989.1

UniProtKB/TrEMBL

A0A0G2JL76, A0A1U9X8K7

Related

ENSP00000444109.1, ENST00000544672.5

Conserved Domains (1) summary

pfam04515
Location:238 → 598

Choline_transpo; Plasma-membrane choline transporter
NM_025257.3 → NP_079533.2 choline transporter-like protein 4 isoform 1

See identical proteins and their annotated locations for NP_079533.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AI560195, AK222998, BC014659, DA924720, DC300771

Consensus CDS

CCDS4724.2

UniProtKB/Swiss-Prot

A2BED3, B0UXX8, B0UZY8, B4DU94, B4DWM2, E9PEK7, Q53GD3, Q5JP84, Q5JQ93, Q658S8, Q6UX89, Q8TEW4, Q96C58, Q96K59, Q9Y332

UniProtKB/TrEMBL

A0A0G2JL76, A0A140VJH4

Related

ENSP00000229729.6, ENST00000229729.11

Conserved Domains (1) summary

pfam04515
Location:313 → 674

Choline_transpo; Plasma-membrane choline transporter