EMC4

protein-coding

ER membrane protein complex subunit 4, the group of ER membrane protein complex subunits

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. Part of EMC complex. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

TMEM85

MANE transcript

NM_016454.4

Inheritance

—

ClinVar variants

U:13B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr15:34,225,013-34,230,156

External References & Databases

Ensembl (ENSG00000128463)

Transcript & Mutation Effects

hg38 • Region Span ~5.1 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 EMC4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 10

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016454.4. 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						0
missense			11 clinvar	1 clinvar		12
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	13	1	0	14

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016454.4	RefSeq	NP_057538.1	5	MANE Select
ENST00000267750.9	Ensembl	ENSP00000267750.4	5	MANE Select
NM_001286420.2	RefSeq	NP_001273349.1	4	Standard
NM_001351373.2	RefSeq	NP_001338302.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

apoptotic process
protein folding in endoplasmic reticulum

Cellular Component

integral component of membrane
ER membrane protein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000267750
Coding exons: 5
Length: 5158
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.28	68	105	0.648	0.00000517	1189
Missense (PolyPhen)		22	33.005	0.66657		372
Synonymous	-0.574	42	37.5	1.12	0.00000186	355
Loss of Function	2.77	1	10.8	0.0922	5.52e-7	113

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.00029	0.00029	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May mediate anti-apoptotic activity.;

Recessive Scores

pRec: 0.130

Intolerance Scores

RVIS EVS: 0.1
RVIS percentile EVS: 61.28

Essentials

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

Gene Damage Prediction

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