TPRN

Chr 9AR

taperin

Also known as: C9orf75, DFNB79

NCBI Gene: 286262ENSG00000176058UniProt: Q4KMQ1

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]

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 79MIM #613307
AR
529
ClinVar variants
126
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— TPRN
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
126 Pathogenic / Likely Pathogenic· 239 VUS of 529 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.007
Z-score 2.13
OE 0.40 (0.22–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.50Z-score
OE missense 1.08 (0.99–1.19)
307 obs / 283.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.22–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (0.99–1.19)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 6 / 14.9Missense obs/exp: 307 / 283.5Syn Z: -1.91

ClinVar Variant Classifications

529 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic106
Likely Pathogenic20
VUS239
Likely Benign114
Benign19
Conflicting31
106
Pathogenic
20
Likely Pathogenic
239
VUS
114
Likely Benign
19
Benign
31
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
91
0
106
Likely Pathogenic
11
0
9
0
20
VUS
0
203
31
5
239
Likely Benign
0
8
20
86
114
Benign
0
4
9
6
19
Conflicting
—31
Total2621516097529

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

View in ClinVar →

Protein Context — Lollipop Plot

TPRN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TPRN-related deafness

definitive
ARLoss Of FunctionAbsent Gene Product
Ear
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TAPERIN; TPRN
MIM #613354 · *

Deafness, autosomal recessive 79

MIM #613307

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TPRN
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools