EMC1

ER membrane protein complex subunit 1, the group of ER membrane protein complex subunits

Basic information

Region (hg38): 1:19215660-19251552

Previous symbols: [ "KIAA0090" ]

Links

ENSG00000127463 ∙ NCBI:23065 ∙ OMIM:616846 ∙ HGNC:28957 ∙ Uniprot:Q8N766 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebellar atrophy, visual impairment, and psychomotor retardation; (Moderate), mode of inheritance: AR
• global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome (Supportive), mode of inheritance: AD
• cerebellar atrophy, visual impairment, and psychomotor retardation; (Strong), mode of inheritance: AR
• complex neurodevelopmental disorder with motor features (Moderate), mode of inheritance: AR
• complex neurodevelopmental disorder with motor features (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebellar atrophy, visual impairment, and psychomotor retardation	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Ophthalmologic	26942288

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EMC1 gene.

• not provided (40 variants)
• Cerebellar atrophy, visual impairment, and psychomotor retardation; (2 variants)
• Obesity (1 variants)
• EMC1-related disorder (1 variants)
• Retinal dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EMC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	14	236	7	258
missense		4	544	10	6	564
nonsense	17	5	2			24
start loss	2	1				3
frameshift	23	2	6			31
inframe indel			15			15
splice donor/acceptor (+/-2bp)		26	2			28
splice region			39	46	5	90
non coding			12	118	12	142
Total	42	39	595	364	25

Highest pathogenic variant AF is 0.0000460

Variants in EMC1

This is a list of pathogenic ClinVar variants found in the EMC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-19219307-C-T		Inborn genetic diseases	Uncertain significance (Jan 26, 2025)
1-19219308-G-A			Uncertain significance (Apr 10, 2024)
1-19219312-G-C			Likely benign (Apr 17, 2021)
1-19219316-C-T			Uncertain significance (Oct 28, 2024)
1-19219316-C-CG			Uncertain significance (Aug 30, 2023)
1-19219317-G-A			Uncertain significance (Feb 17, 2024)
1-19219317-G-T			Likely benign (Oct 20, 2024)
1-19219318-A-G			Likely benign (Dec 05, 2024)
1-19219321-C-G		not specified	Likely benign (Jan 22, 2024)
1-19219327-C-T			Likely benign (Aug 27, 2023)
1-19219330-C-T			Likely benign (Sep 17, 2021)
1-19219329-T-TCA			Likely pathogenic (Jun 22, 2018)
1-19219336-T-C			Likely benign (Dec 07, 2024)
1-19219345-C-T			Likely benign (Jul 01, 2022)
1-19219349-G-A		Inborn genetic diseases	Uncertain significance (Nov 28, 2024)
1-19219349-G-GTGA			Uncertain significance (Apr 18, 2023)
1-19219355-A-G			Uncertain significance (Nov 05, 2024)
1-19219357-G-T			Likely benign (Sep 27, 2022)
1-19219358-G-A			Uncertain significance (Sep 05, 2024)
1-19219372-G-A			Likely benign (Nov 18, 2024)
1-19219373-C-A			Uncertain significance (Dec 05, 2022)
1-19219376-A-G			Uncertain significance (Feb 05, 2022)
1-19219383-C-T			Uncertain significance (Mar 16, 2024)
1-19219384-G-A			Likely benign (May 18, 2023)
1-19219385-C-G			Uncertain significance (May 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EMC1	protein_coding	protein_coding	ENST00000477853	23	35889

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.73e-26	0.0359	125582	0	166	125748	0.000660

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.35	493	585	0.843	0.0000345	6421
Missense in Polyphen		150	197.13	0.76093		2068
Synonymous	1.54	205	235	0.872	0.0000137	2037
Loss of Function	1.49	46	58.3	0.789	0.00000314	599

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00142	0.00142
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000653	0.000653
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000669	0.000668
Middle Eastern	0.000653	0.000653
South Asian	0.000980	0.000980
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Cerebellar atrophy, visual impairment, and psychomotor retardation (CAVIPMR) [MIM:616875]: An autosomal recessive, neurodegenerative disorder characterized by developmental delay, intellectual disability, hypotonia, scoliosis, cerebellar atrophy, and variable dysmorphic features. {ECO:0000269|PubMed:26942288}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.113

Haploinsufficiency Scores

• pHI: 0.498
• hipred: N
• hipred_score: 0.333
• ghis: 0.590

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Emc1

Gene ontology

• Biological process: protein folding in endoplasmic reticulum
• Cellular component: integral component of membrane;protein-containing complex;ER membrane protein complex