TPRN

Chr 9AR

taperin

Also known as: C9orf75, DFNB79

NCBI Gene: 286262 ENSG00000176058 UniProt: Q4KMQ1 OMIM: 613354

The TPRN protein is essential for hearing and required for maintenance of stereocilia on inner and outer hair cells, where it forms rings at the base of stereocilia and binds actin filaments to stabilize these structures. Mutations cause autosomal recessive deafness (DFNB79), affecting auditory function through disruption of hair cell stereocilia integrity. This gene follows autosomal recessive inheritance and is not highly constrained against loss-of-function variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This locus encodes a sensory epithelial protein. It was defined by linkage analysis in three Pakistani families to lie between D9S1818 (centromeric) and D9SH6 (telomeric). Mutations at this locus have been associated with autosomal recessive deafness. [provided by RefSeq, Oct 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.801 OMIM phenotype

Clinical Summary— TPRN

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

33 unique Pathogenic / Likely Pathogenic· 231 VUS of 427 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — TPRN

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.007

Z-score 2.13

OE 0.40 (0.22–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.50Z-score

OE missense 1.08 (0.99–1.19)

307 obs / 283.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.40 (0.22–0.80)

0≤0.351.4

Missense OE?1.08 (0.99–1.19)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 6 / 14.9Missense obs/exp: 307 / 283.5Syn Z: -1.91

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveTPRN-related deafnessLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6164th %ile

GOF

0.6932th %ile

LOF

0.3940th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

427 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic13

VUS231

Likely Benign115

Benign17

Conflicting28

Pathogenic

Likely Pathogenic

231

VUS

115

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	20	0	0	0	20
Likely Pathogenic	13	0	0	0	13
VUS	0	219	7	5	231
Likely Benign	0	11	17	87	115
Benign	0	7	5	5	17
Conflicting	—				28
Total	33	237	29	97	424

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

View in ClinVar →

93 pathogenic / likely-pathogenic (of 107) ClinVar copy-number / structural variants overlap TPRN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →