PROK2
Chr 3ADARprokineticin 2
Also known as: BV8, HH4, KAL4, MIT1, PK2
This gene encodes prokineticin 2, a secreted protein that functions as an output molecule from the suprachiasmatic nucleus to transmit circadian behavioral rhythms and also contracts gastrointestinal smooth muscle. Mutations cause hypogonadotropic hypogonadism with or without anosmia (Kallmann syndrome), involving defective puberty and often absent sense of smell. The condition shows both autosomal dominant and autosomal recessive inheritance patterns.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
114 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 1 | 15 | 0 | 17 |
Likely Pathogenic | 4 | 3 | 1 | 0 | 8 |
VUS | 2 | 33 | 11 | 1 | 47 |
Likely Benign | 0 | 2 | 15 | 7 | 24 |
Benign | 0 | 1 | 9 | 0 | 10 |
Conflicting | — | 5 | |||
| Total | 7 | 40 | 51 | 8 | 111 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PROK2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools