PKHD1

Chr 6

PKHD1 ciliary IPT domain containing fibrocystin/polyductin

Also known as: ARPKD, FCYT, FPC, PCYT, PKD4, TIGM1

The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.68
Clinical SummaryPKHD1
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Gene-Disease Validity (ClinGen)
autosomal recessive polycystic kidney disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.68LOEUF
pLI 0.000
Z-score 5.28
OE 0.58 (0.490.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.98Z-score
OE missense 1.06 (1.021.10)
2245 obs / 2117.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.58 (0.490.68)
00.351.4
Missense OE?1.06 (1.021.10)
00.61.4
Synonymous OE?1.03
01.21.6
LoF obs/exp: 107 / 184.4Missense obs/exp: 2245 / 2117.9Syn Z: -0.56
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePKHD1-related polycystic kidney diseaseLOFAR

This gene — mechanism propensity

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

DN
0.6745th %ile
GOF
0.5169th %ile
LOF
0.3746th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PKHD1 · protein map & ClinVar variants

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