TNMD

protein-coding

tenomodulin, the group of BRICHOS domain containing

Gene summary

This gene encodes a protein that is related to chondromodulin-I, which is a cartilage-specific glycoprotein that functions to stimulate chondrocyte growth and to inhibit tube formation of endothelial cells. This protein is also an angiogenesis inhibitor. Genetic variation in this gene is associated with a risk for type 2 diabetes, central obesity and serum levels of systemic immune mediators in a body size-dependent manner. This gene is also a candidate gene for age-related macular degeneration, though a direct link has yet to be demonstrated. [provided by RefSeq, Sep 2009]

MANE transcript

NM_022144.3

Inheritance

—

ClinVar variants

U:33B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chrX:100,584,936-100,599,885

External References & Databases

Ensembl (ENSG00000000005)

Transcript & Mutation Effects

hg38 • Region Span ~14.9 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 TNMD variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022144.3. 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			2 clinvar	3 clinvar	2 clinvar	7
missense			31 clinvar	1 clinvar		32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	33	4	2	39

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022144.3	RefSeq	NP_071427.2	7	MANE Select
ENST00000373031.5	Ensembl	ENSP00000362122.4	7	MANE Select
ENST00001132607.1	Ensembl	ENSP00000810151.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

endothelial cell morphogenesis
negative regulation of endothelial cell proliferation
negative regulation of angiogenesis
negative regulation of vascular endothelial growth factor receptor signaling pathway
tendon cell differentiation

Molecular Function

protein binding

Cellular Component

nuclear envelope
cytoplasm
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373031
Coding exons: 7
Length: 15084
Individuals with no LoFs: 125726
Homozygous LoFs: 4
Heterozygous LoFs: 7
Defined: 125737
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.859	93	119	0.779	0.00000930	2099
Missense (PolyPhen)		31	49.343	0.62826		758
Synonymous	-0.464	42	38.3	1.10	0.00000299	551
Loss of Function	1.80	6	13.0	0.461	0.00000109	221

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0.000037	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000075	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000074	0.000053	rare
South Asian	0.00011	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be an angiogenesis inhibitor.;

Recessive Scores

pRec: 0.210

Intolerance Scores

LoFtool: 0.425
RVIS EVS: -0.05
RVIS percentile EVS: 49.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0910

Gene Damage Prediction

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