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…

LOEUF 0.38

Clinical Summary— TLNRD1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

59 VUS of 64 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.914

Z-score 2.60

OE 0.00 (0.00–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.06Z-score

OE missense 0.61 (0.53–0.71)

139 obs / 226.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.38)

0≤0.351.4

Missense OE?0.61 (0.53–0.71)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 0 / 7.9Missense obs/exp: 139 / 226.3Syn Z: 0.77

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

VUS59

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	59	0	59
Likely Benign	2	3	5
Benign	0	0	0
Total	61	3	64

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

22 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap TLNRD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →