PKHD1

Chr 6AR

PKHD1 ciliary IPT domain containing fibrocystin/polyductin

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

The protein encoded by PKHD1 promotes ciliogenesis in renal epithelial cells, regulates centrosome duplication and mitotic spindle assembly, and participates in collecting-duct and biliary differentiation. Mutations cause autosomal recessive polycystic kidney disease with or without hepatic disease, typically presenting in infancy or childhood with enlarged cystic kidneys and potential liver involvement. This gene follows autosomal recessive inheritance and is highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.681 OMIM phenotype
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

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 OE0.58 (0.490.68)
00.351.4
Missense OE1.06 (1.021.10)
00.61.4
Synonymous OE1.03
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

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.

3D Protein StructureAlphaFold
Clinical Literature
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