TMTC1

protein-coding

transmembrane O-mannosyltransferase targeting cadherins 1, the group of Tetratricopeptide repeat domain containing|Transmembrane and tetratricopeptide repeat containing

Gene summary

Enables dolichyl-phosphate-mannose-protein mannosyltransferase activity. Involved in protein O-linked glycosylation via mannose. Predicted to be located in endoplasmic reticulum and membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001193451.2

Inheritance

—

ClinVar variants

U:139B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr12:29,500,840-29,784,759

External References & Databases

Ensembl (ENSG00000133687)

Transcript & Mutation Effects

hg38 • Region Span ~283.9 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 TMTC1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 132

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001193451.2. 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	3 clinvar	2 clinvar	6
missense			131 clinvar	6 clinvar		137
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	139	9	2	150

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 62 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001193451.2	RefSeq	NP_001180380.1	18	MANE Select
ENST00000539277.6	Ensembl	ENSP00000442046.1	18	MANE Select
NM_001367875.2	RefSeq	NP_001354804.1	20	Standard
NM_175861.3	RefSeq	NP_787057.2	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

RNA processing

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000539277
Coding exons: 18
Length: 283920
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 57
Defined: 125748
p: 0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.711	409	452	0.906	0.0000240	5674
Missense (PolyPhen)		132	175.19	0.75346		2062
Synonymous	-0.671	188	177	1.06	0.00000968	1737
Loss of Function	3.06	22	43.9	0.501	0.00000221	543

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00025	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00038	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00016	0.00016	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.785
RVIS EVS: -0.42
RVIS percentile EVS: 25.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.367

Gene Damage Prediction

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