PKHD1L1

Chr 8AR

PKHD1 like 1

Also known as: DFNB124, PKHDL1

This protein is a component of hair-cell stereocilia coat that is required for normal hearing. Mutations cause autosomal recessive nonsyndromic deafness (DFNB124), affecting the auditory system specifically. The gene shows no constraint against loss-of-function variants (pLI near zero), consistent with its autosomal recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 124MIM #620794
AR
0
Active trials
7
Pubs (1 yr)
37
P/LP submissions
0%
P/LP missense
1.06
LOEUF
Mechanism
Clinical SummaryPKHD1L1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 unique Pathogenic / Likely Pathogenic· 367 VUS of 477 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.06LOEUF
pLI 0.000
Z-score 0.86
OE 0.93 (0.821.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.72Z-score
OE missense 1.04 (1.011.08)
2145 obs / 2053.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.93 (0.821.06)
00.351.4
Missense OE1.04 (1.011.08)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 174 / 186.6Missense obs/exp: 2145 / 2053.3Syn Z: -0.63

ClinVar Variant Classifications

477 submitted variants in ClinVar

Classification Summary

Pathogenic37
VUS367
Likely Benign32
Benign6
Conflicting1
37
Pathogenic
367
VUS
32
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
0
0
0
VUS
1
362
4
0
367
Likely Benign
1
26
1
4
32
Benign
0
4
0
2
6
Conflicting
1
Total2392426443

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

View in ClinVar →

Protein Context — Lollipop Plot

PKHD1L1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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