TMEM74

protein-coding

transmembrane protein 74

Gene summary

Predicted to enable transmembrane transporter binding activity. Involved in macroautophagy. Predicted to be located in cytoplasmic vesicle; plasma membrane; and vacuolar membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_153015.3

Inheritance

—

ClinVar variants

U:37B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr8:108,606,850-108,787,594

External References & Databases

Ensembl (ENSG00000164841)

Transcript & Mutation Effects

hg38 • Region Span ~180.7 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 TMEM74 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 38

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153015.3. 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			37 clinvar	1 clinvar		38
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	37	1	0	38

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153015.3	RefSeq	NP_694560.1	1	MANE Select
ENST00000297459.4	Ensembl	ENSP00000297459.3	1	MANE Select
ENST00000899500.1	Ensembl	ENSP00000569559.1	1	Standard
ENST00000899500.2	Ensembl	ENSP00000569559.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

macroautophagy

Molecular Function

protein binding

Cellular Component

autophagosome membrane
lysosomal membrane
integral component of membrane
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000297459
Coding exons: 1
Length: 180766
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125748
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0535	176	178	0.989	0.0000103	1992
Missense (PolyPhen)		50	57.426	0.87068		630
Synonymous	0.413	66	70.4	0.937	0.00000392	628
Loss of Function	0.646	6	7.97	0.753	4.00e-7	102

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.00020	0.00020	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an essential role in autophagy. TMEM74-induced autophagy may involve PI3K signal transduction. {ECO:0000269|PubMed:18294959, ECO:0000269|PubMed:19029833}.;

Recessive Scores

pRec: 0.0991

Intolerance Scores

LoFtool: 0.271
RVIS EVS: -0.36
RVIS percentile EVS: 28.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.168

Gene Damage Prediction

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