GeneBe

NHLRC2

protein-coding

NHL repeat containing 2

Gene summary

Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_198514.4

Inheritance

AR

ClinVar variants

P:14U:89B:27

Top phenotype

Fibrosis, neurodegeneration, and cerebral angiomatosis

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr10:113,854,661-113,917,194

External References & Databases

Ensembl (ENSG00000196865)NCBI Gene (374354)OMIM (618277)HGNC:24731GenCCUniProt (Q8NBF2)AlphaFoldClinVar (NHLRC2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~62.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

fibrosis, neurodegeneration, and cerebral angiomatosisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032651

Submitter: Ambry Genetics

fibrosis, neurodegeneration, and cerebral angiomatosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032651

Submitter: PanelApp Australia

fibrosis, neurodegeneration, and cerebral angiomatosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032651

Submitter: Labcorp Genetics (formerly Invitae)

fibrosis, neurodegeneration, and cerebral angiomatosisDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0032651

Submitter: G2P

Clinical Genomic Database (CGD)

Fibrosis, neurodegeneration, and cerebral angiomatosisAR

Manifestation: Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Pulmonary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29423877Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NHLRC2 variants in ClinVar

6 Conditions Cataloged
Inborn genetic diseasesTotal: 78
Fibrosis, neurodegeneration, and cerebral angiomatosisTotal: 22
NHLRC2-related disorderTotal: 21
not providedTotal: 20
not specifiedTotal: 10
See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198514.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
16
clinvar
 17
missense
3
clinvar
2
clinvar
85
clinvar
8
clinvar
3
clinvar
 101
nonsense
1
clinvar
2
clinvar
 3
start loss
1
clinvar
 1
frameshift
2
clinvar
5
clinvar
 7
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total6889243130

Highest pathogenic variant AF is 0.00023051184

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_198514.4RefSeqNP_940916.211MANE Select
ENST00000369301.3EnsemblENSP00000358307.311MANE Select
ENST00000866165.1EnsemblENSP00000536224.110Standard
ENST00000866165.2EnsemblENSP00000536224.110Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
nhlrc2Danio rerio

Structure: midbrain

Quality: vacuolated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Platelet degranulation
  • Response to elevated platelet cytosolic Ca2+
  • Platelet activation, signaling and aggregation
  • Hemostasis

Biological Process

  • platelet degranulation
  • cell redox homeostasis

Molecular Function

  • protein binding

Cellular Component

  • extracellular region
  • platelet alpha granule lumen

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000369301
Coding exons
11
Length
62534
Individuals with no LoFs
125703
Homozygous LoFs
0
Heterozygous LoFs
42
Defined
125745
p
0.000167
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.7423283680.8910.00001694705
Missense (PolyPhen)70112.770.620741468
Synonymous0.08971371380.9900.000006741420
Loss of Function2.951432.00.4370.00000148425

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000200.00020rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000260.00025rare
South Asian0.0000990.000098rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec
0.0994

Intolerance Scores

LoFtool
0.467
RVIS EVS
0.67
RVIS percentile EVS
84.61

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
N
Indispensability score
0.294

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.