TLNRD1

Chr 15

talin rod domain containing 1

Also known as: MESDC1

NCBI Gene: 59274 ENSG00000140406 UniProt: Q9H1K6 OMIM: 615466

This gene encodes an actin-binding protein that regulates cell proliferation, migration and invasion. The gene is highly constrained against loss-of-function variants (pLI 0.91, LOEUF 0.38), suggesting that mutations would likely cause severe developmental phenotypes, but no specific human genetic disorders have been definitively associated with TLNRD1 mutations to date. Based on mouse studies showing expression during early development and roles in mesoderm differentiation affecting heart, muscle, blood, skeleton and urogenital systems, mutations would be expected to cause multi-system developmental abnormalities.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that is regulated by micro RNA MiR-574-3, and is thought to have an oncogenic function in human bladder cancer. A similar gene in mouse is located in a chromosomal region critical for differentiation of mesoderm, which affects embryo patterning and the formation of heart, muscle, blood, skeleton and the urogenital system. The mouse gene is expressed in early development, and in the adult. [provided by RefSeq, Nov 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in TLNRD1?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

613 rare PASS variants

Rare truncating (LoF)

1 in 8,400

45 rare PASS variants

Rare synonymous (reference)

1 in 120

369 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TLNRD1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 7,800
South Asian	~43k	1 in 130	1 in 6,600
Remaining (unassigned)	~30k	1 in 220	≈ 1 in 29,000
European (Finnish)	~26k	1 in 470	≈ 1 in 7,000
Admixed American	~22k	1 in 230	≈ 1 in 5,100
African / African American	~21k	1 in 190	≈ 1 in 21,000
East Asian	~20k	1 in 180	≈ 1 in 8,400
Ashkenazi Jewish	~13k	1 in 670	≈ 1 in 9,900
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,600

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.