NID2

Chr 14

nidogen 2

Also known as: NID-2

NCBI Gene: 22795ENSG00000087303UniProt: Q14112

This gene encodes a member of the nidogen family of basement membrane proteins. This protein is a cell-adhesion protein that binds collagens I and IV and laminin and may be involved in maintaining the structure of the basement membrane.[provided by RefSeq, Jun 2010]

295
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NID2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 246 VUS of 295 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.56LOEUF
pLI 0.000
Z-score 4.45
OE 0.40 (0.29–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.25Z-score
OE missense 1.02 (0.97–1.08)
826 obs / 806.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.29–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.97–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 26 / 64.6Missense obs/exp: 826 / 806.1Syn Z: -1.30

ClinVar Variant Classifications

295 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS246
Likely Benign27
Benign12
Conflicting1
8
Pathogenic
1
Likely Pathogenic
246
VUS
27
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
245
1
0
246
Likely Benign
0
19
0
8
27
Benign
0
7
1
4
12
Conflicting
—1
Total02711112295

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

View in ClinVar →

Protein Context — Lollipop Plot

NID2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
NIDOGEN 2; NID2
MIM #605399 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis.
Kathuria I et al.·Int J Mol Sci
2024
NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva.
Guerrero-Preston R et al.·Cancer Prev Res (Phila)
2011
Angiogenesis-related gene NID2 profiling and immune infiltration in bladder cancer: prognostic implications and immunotherapy response.
Cao J et al.·Front Immunol
2025
Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma.
Chai AW et al.·Oncotarget
2016
Multi-institutional external validation of urinary TWIST1 and NID2 methylation as a diagnostic test for bladder cancer.
Fantony JJ et al.·Urol Oncol
2015
Identification of basement membrane-related biomarkers associated with the diagnosis of osteoarthritis based on machine learning.
Huang X et al.·BMC Med Genomics
2023
Transcriptomic Features of Recurrence Rates in Idiopathic Subglottic Stenosis.
Ying S et al.·Laryngoscope
2025
Towards the identification of a genetic basis for Landau-Kleffner syndrome.
Conroy J et al.·Epilepsia
2014
Clinical performance and utility of a DNA methylation urine test for bladder cancer.
Abern MR et al.·Urol Oncol
2014
Rare Variant Analysis and Molecular Dynamics Simulation in Alzheimer's Disease Identifies Exonic Variants in FLG.
Xiong W et al.·Genes (Basel)
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools