PCNX2

Chr 1

pecanex 2

Also known as: PCNXL2

NCBI Gene: 80003 ENSG00000135749 UniProt: A6NKB5 OMIM: 617656

PCNX2 encodes a protein that may be involved in preventing tumorigenesis in colorectal tissue with high microsatellite instability. The gene is not highly constrained to loss-of-function variation and defects are associated with colorectal carcinomas rather than pediatric neurological disorders. Based on the available information, this gene does not appear to have established associations with inherited neurogenetic conditions in children.

OMIM ResearchSummary from RefSeq, UniProt

This gene contains coding mononucleotide repeats that are associated with tumors of high mcrosatellite instability (MSI-H). Defects in this gene are involved in the tumorigenesis of MSI-H colorectal carcinomas. [provided by RefSeq, Jun 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.68

Clinical Summary— PCNX2

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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

25 VUS of 85 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.000

Z-score 4.23

OE 0.54 (0.43–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.21Z-score

OE missense 0.90 (0.86–0.95)

1065 obs / 1181.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.43–0.68)

0≤0.351.4

Missense OE?0.90 (0.86–0.95)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 54 / 99.5Missense obs/exp: 1065 / 1181.7Syn Z: -0.09

This gene — mechanism propensity

0.6551th %ile

GOF

0.6932th %ile

LOF

0.4233th %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

85 submitted variants in ClinVar

ClinVar

Classification Summary

VUS25

Likely Benign7

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	24	0	1	25
Likely Benign	3	1	3	7
Benign	0	1	0	1
Total	27	2	4	33

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap PCNX2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →