SMCR8 SMCR8-C9orf72 complex subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: SMCR8provided by HGNC
Official Full Name: SMCR8-C9orf72 complex subunitprovided by HGNC
Primary source: HGNC:HGNC:17921
See related: Ensembl:ENSG00000176994 MIM:617074; AllianceGenome:HGNC:17921
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DENND8A
Summary: Enables GTPase activator activity; protein kinase binding activity; and protein kinase inhibitor activity. Contributes to guanyl-nucleotide exchange factor activity. Involved in negative regulation of gene expression; regulation of TOR signaling; and regulation of macroautophagy. Located in Atg1/ULK1 kinase complex; chromatin; and nucleoplasm. Part of guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in bone marrow (RPKM 10.7), spleen (RPKM 8.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17p11.2

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (18315293..18328056)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (18262099..18274862)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (18218607..18231370)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ALS-linked C9orf72-SMCR8 complex is a negative regulator of primary ciliogenesis.
Title: ALS-linked C9orf72-SMCR8 complex is a negative regulator of primary ciliogenesis.
C9orf72-associated SMCR8 protein binds in the ubiquitin pathway and with proteins linked with neurological disease.
Title: C9orf72-associated SMCR8 protein binds in the ubiquitin pathway and with proteins linked with neurological disease.
Structure of the C9orf72 ARF GAP complex that is haploinsufficient in ALS and FTD.
Title: Structure of the C9orf72 ARF GAP complex that is haploinsufficient in ALS and FTD.
Our study not only illustrates the basis of C9ORF72-SMCR8-WDR41 complex assembly but also reveals the GAP activity of the C9ORF72-SMCR8 complex
Title: Cryo-EM structure of C9ORF72-SMCR8-WDR41 reveals the role as a GAP for Rab8a and Rab11a.
While focusing on the role of SMCR8 during autophagy initiation, we found that kinase activity and gene expression of ULK1 are increased upon SMCR8 depletion. The latter phenotype involved association of SMCR8 with the ULK1 gene locus.
Title: Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator.
Study describes the identification of two binding partners for C9orf72: SMCR8 and WDR41 and demonstrated that C9orf72/SMCR8/WDR41 interacts with the FIP200/Ulk1/ATG13/ATG101 complex.
Title: The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway.

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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

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

RH15951 (e-PCR)
- UniSTS:59905

SMCR8__6860 (e-PCR)
- UniSTS:466459

G33160 (e-PCR)
- UniSTS:57951

SHMT1_8625 (e-PCR)
- UniSTS:468691

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTPase activator activity	IMP Inferred from Mutant Phenotype more info	PubMed
contributes_to guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in autophagy	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of autophagosome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of exocytosis	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of macroautophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of TOR signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of autophagosome maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of TORC1 signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of autophagy	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of Atg1/ULK1 kinase complex	IDA Inferred from Direct Assay more info	PubMed
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	NAS Non-traceable Author Statement more info	PubMed
part_of guanyl-nucleotide exchange factor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of guanyl-nucleotide exchange factor complex	IDA Inferred from Direct Assay more info	PubMed
part_of guanyl-nucleotide exchange factor complex	IPI Inferred from Physical Interaction more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in postsynapse	ISS Inferred from Sequence or Structural Similarity more info
located_in presynapse	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: guanine nucleotide exchange protein SMCR8

Names: Smith-Magenis syndrome chromosome region, candidate 8; smith-Magenis syndrome chromosomal region candidate gene 8 protein

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.