EMC10
protein-codingER membrane protein complex subunit 10, the group of ER membrane protein complex subunits
Gene summary
Contributes to membrane insertase activity. Involved in positive regulation of angiogenesis; positive regulation of endothelial cell proliferation; and protein insertion into ER membrane. Located in endoplasmic reticulum membrane and extracellular region. Part of EMC complex. [provided by Alliance of Genome Resources, Jul 2025]
- C19orf63
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0031011
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0700092
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0031011
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0032680
Submitter: Franklin by Genoox
a Saudi family with two individuals segregating a recessive neurodevelopmental disorder. Both of the affected individuals showed mild ID, speech delay, and GDD. Whole‚Äêexome sequencing (WES) and Sanger sequencing were performed to identify candidate genes. Further, to elucidate the functional effects of the variant, quantitative real‚Äêtime PCR (RT‚ÄêqPCR)‚Äêbased expression analysis was performed. WES revealed a homozygous splice acceptor site variant (c.679‚Äê1G>A) in EMC10 (chromosome 19q13.33) that segregated perfectly within the family. RT‚ÄêqPCR showed a substantial decrease in the relative EMC10 gene expression in the patients, indicating the pathogenicity of the identified variant. https://onlinelibrary.wiley.com/doi/10.1111/cge.13842
Inheritance Pattern: AR
Disease ID:MONDO:0031011
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
Intervention: General
Rationale: 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
Comments: Renal anomalies have been described in some individuals, but it is unclear if these are related to EMC10
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EMC10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_206538.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 6 | 9 | |||
| missense | 48 | 5 | 1 | 54 | ||
| nonsense | 2 | 5 | 7 | |||
| start loss | 1 | 1 | 2 | |||
| frameshift | 3 | 3 | 6 | |||
| splice donor/acceptor (+/-2bp) | 3 | 2 | 3 | 8 | ||
| Total | 8 | 11 | 55 | 11 | 1 | 86 |
Highest pathogenic variant AF is 0.00010907829
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_996261.1 | 7 | MANE Select | |
| Ensembl | ENSP00000334037.6 | 7 | MANE Select | |
| RefSeq | NP_778233.4 | 7 | Standard | |
| Ensembl | ENSP00000366117.2 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- angiogenesis
- positive regulation of endothelial cell proliferation
- positive regulation of endothelial cell migration
- positive regulation of angiogenesis
- positive regulation of p38MAPK cascade
Cellular Component
- extracellular region
- integral component of membrane
- ER membrane protein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334976
- Coding exons
- 7
- Length
- 6952
- Individuals with no LoFs
- 125660
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 68
- Defined
- 125728
- p
- 0.000270
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.110 | 152 | 156 | 0.975 | 0.0000103 | 1581 |
| Missense (PolyPhen) | 59 | 60.117 | 0.98142 | 600 | ||
| Synonymous | -0.849 | 81 | 71.8 | 1.13 | 0.00000480 | 570 |
| Loss of Function | -0.178 | 15 | 14.3 | 1.05 | 9.40e-7 | 128 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00031 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00023 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00035 | 0.00033 | rare |
| South Asian | 0.00048 | 0.00046 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Promotes angiogenesis and tissue repair in the heart after myocardial infarction. Stimulates cardiac endothelial cell migration and outgrowth via the activation of p38 MAPK, PAK and MAPK2 signaling pathways. {ECO:0000269|PubMed:28931551}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.99
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |