PNCK

Chr X

pregnancy up-regulated nonubiquitous CaM kinase

Also known as: BSTK3, CaMK1b

NCBI Gene: 139728 ENSG00000130822 UniProt: Q6P2M8 OMIM: 300680

PNCK is a member of the calcium/calmodulin-dependent protein kinase family of protein serine/threonine kinases (see CAMK1; MIM 604998) (Gardner et al., 2000 [PubMed 10673339]).[supplied by OMIM, Mar 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.10

Clinical Summary— PNCK

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

31 VUS of 63 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.000

Z-score 1.29

OE 0.65 (0.40–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.51Z-score

OE missense 0.69 (0.60–0.80)

132 obs / 190.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.40–1.10)

0≤0.351.4

Missense OE?0.69 (0.60–0.80)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 15.5Missense obs/exp: 132 / 190.6Syn Z: -0.03

This gene — mechanism propensity

0.74top 25%

GOF

0.78top 25%

LOF

0.2483th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

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

63 submitted variants in ClinVar

ClinVar

Classification Summary

VUS31

Likely Benign5

Benign2

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	31	0	0	31
Likely Benign	0	3	1	1	5
Benign	0	0	1	1	2
Conflicting	—				1
Total	0	34	2	2	39

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

View in ClinVar →

119 pathogenic / likely-pathogenic (of 138) ClinVar copy-number / structural variants overlap PNCK — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →