NHLRC2

Chr 10

NHL repeat containing 2

NCBI Gene: 374354ENSG00000196865UniProt: Q8NBF2

Required for normal embryonic development

Primary Disease Associations & Inheritance

UniProtFibrosis, neurodegeneration, and cerebral angiomatosis
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NHLRC2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.68LOEUF
pLI 0.000
Z-score 2.95
OE 0.44 (0.29–0.68)
Tolerant

Typical tolerance to LoF variation

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.
0.74Z-score
OE missense 0.89 (0.81–0.98)
328 obs / 368.1 exp
Tolerant

Mild missense constraint

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.0.44 (0.29–0.68)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.81–0.98)
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.0.99
0≤1.21.6
LoF obs/exp: 14 / 32.0Missense obs/exp: 328 / 368.1Syn Z: 0.09

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NHLRC2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NHLRC2-related fibrosis, neurodegeneration, and cerebral angiomatosis

definitive
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Variant in NHLRC2 leads to increased hnRNP C2 in developing neurons and the hippocampus of a mouse model of FINCA disease.
Hiltunen AE et al.·Mol Med
2020Functional
Broadening the phenotypic and molecular spectrum of FINCA syndrome: Biallelic NHLRC2 variants in 15 novel individuals.
Sczakiel HL et al.·Eur J Hum Genet
2023
NHLRC2 expression is increased in idiopathic pulmonary fibrosis.
Kreus M et al.·Respir Res
2022
Expanding the phenotypic spectrum of FINCA (fibrosis, neurodegeneration, and cerebral angiomatosis) syndrome beyond infancy.
Rapp CK et al.·Clin Genet
2021Review
Case report: novel mutations of NDUFS6 and NHLRC2 genes potentially cause the quick postnatal death of a Chinese Hani minority neonate with mitochondrial complex I deficiency and FINCA syndrome.
Li Y et al.·Medicine (Baltimore)
2022Case report
Association of antihypertensive drug target genes with stroke subtypes: A Mendelian randomization study.
Zheng H et al.·J Stroke Cerebrovasc Dis
2025
FINCA syndrome-Defining neurobehavioral phenotype in survivors into late childhood.
Badura-Stronka M et al.·Mol Genet Genomic Med
2022
NHLRC2 variants identified in patients with fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA): characterisation of a novel cerebropulmonary disease.
Uusimaa J et al.·Acta Neuropathol
2018Case report
A Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Salmonella Infection.
Yeung ATY et al.·mBio
2019
Novel compound heterozygous variants in NHLRC2 in a patient with FINCA syndrome.
Brodsky NN et al.·J Hum Genet
2020Case report
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.

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External Resources

Links to major genomics databases and tools