TMCC1

protein-coding

transmembrane and coiled-coil domain family 1, the group of Transmembrane and coiled-coil domain containing

Gene summary

Enables identical protein binding activity. Involved in several processes, including endosome fission; endosome membrane tubulation; and membrane fission. Located in cytosol; endoplasmic reticulum-endosome membrane contact site; and rough endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001017395.5

Inheritance

—

ClinVar variants

U:51

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr3:129,647,792-129,893,711

External References & Databases

Ensembl (ENSG00000172765)

Transcript & Mutation Effects

hg38 • Region Span ~245.9 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 TMCC1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 46

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001017395.5. 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			2 clinvar			2
missense			48 clinvar			48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	51	0	0	51

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 88 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001017395.5	RefSeq	NP_001017395.2	4	MANE Select
ENST00000393238.8	Ensembl	ENSP00000376930.3	4	MANE Select
NM_001128224.3	RefSeq	NP_001121696.1	4	Standard
NM_001349263.2	RefSeq	NP_001336192.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

endoplasmic reticulum organization
protein homooligomerization
protein heterooligomerization

Molecular Function

protein binding
protein homodimerization activity
protein heterodimerization activity

Cellular Component

endoplasmic reticulum membrane
rough endoplasmic reticulum
cytosol
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393238
Coding exons: 4
Length: 245785
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125747
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.06	199	363	0.548	0.0000204	4289
Missense (PolyPhen)		42	129.69	0.32385		1630
Synonymous	0.858	126	139	0.907	0.00000750	1308
Loss of Function	3.75	4	23.7	0.169	0.00000136	273

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.453
RVIS EVS: -0.45
RVIS percentile EVS: 24.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.375

Gene Damage Prediction

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