EMC2

protein-coding

ER membrane protein complex subunit 2, the group of ER membrane protein complex subunits|Tetratricopeptide repeat domain containing

Gene summary

Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Located in endoplasmic reticulum membrane. Is extrinsic component of endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KIAA0103
TTC35

MANE transcript

NM_014673.5

Inheritance

—

ClinVar variants

U:33

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr8:108,443,601-108,489,196

External References & Databases

Ensembl (ENSG00000104412)

Transcript & Mutation Effects

hg38 • Region Span ~45.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EMC2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 24

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014673.5. 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			1 clinvar			1
missense			28 clinvar			28
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	33	0	0	33

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014673.5	RefSeq	NP_055488.1	11	MANE Select
ENST00000220853.8	Ensembl	ENSP00000220853.3	11	MANE Select
NM_001329493.2	RefSeq	NP_001316422.1	11	Standard
NM_001329494.2	RefSeq	NP_001316423.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein folding in endoplasmic reticulum

Molecular Function

protein binding

Cellular Component

nucleus
cytoplasm
endoplasmic reticulum
ER membrane protein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000220853
Coding exons: 11
Length: 43316
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.620	128	149	0.857	0.00000725	1957
Missense (PolyPhen)		20	34.633	0.57748		476
Synonymous	-0.407	52	48.4	1.07	0.00000223	493
Loss of Function	2.71	8	21.6	0.371	0.00000106	275

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0	0.0	absent
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.111

Intolerance Scores

RVIS EVS: -0.1
RVIS percentile EVS: 46.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N

Gene Damage Prediction

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