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
• cerebellar atrophy, visual impairment, and psychomotor retardation; (Limited), 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 (1223 variants)
• Inborn_genetic_diseases (139 variants)
• Cerebellar_atrophy,_visual_impairment,_and_psychomotor_retardation%3B (57 variants)
• Retinal_dystrophy (52 variants)
• EMC1-related_disorder (15 variants)
• not_specified (11 variants)
• Global_developmental_delay (2 variants)
• Cerebellar_atrophy (2 variants)
• Obesity (1 variants)
• Microcephaly (1 variants)
• See_cases (1 variants)
• Autosomal_recessive_retinitis_pigmentosa (1 variants)
• Congenital_anomaly_of_kidney_and_urinary_tract (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. These statistics are base on transcript: NM_000015047.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	15	256	6	278
missense	1	8	614	18	4	645
nonsense	19	7	2			28
start loss	2	1				3
frameshift	31	4	6			41
splice donor/acceptor (+/-2bp)		28	3			31
Total	53	49	640	274	10

Highest pathogenic variant AF is 0.00014002305

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