NHSL2

protein-coding

NHS like 2

Gene summary

Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001013627.3

Inheritance

—

ClinVar variants

U:180B:12

Top phenotype

Spinocerebellar ataxia, X-linked

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chrX:71,910,845-72,161,750

External References & Databases

Ensembl (ENSG00000204131)

Transcript & Mutation Effects

hg38 • Region Span ~250.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NHSL2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 231

not providedTotal: 14

Spinocerebellar ataxia, X-linkedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001013627.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	5 clinvar		10
missense			171 clinvar	7 clinvar		178
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	180	12	0	192

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001013627.3	RefSeq	NP_001013649.2	8	MANE Select
ENST00000633930.2	Ensembl	ENSP00000488668.1	8	MANE Select
NM_001438805.1	RefSeq	NP_001425734.1	9	Standard
NM_001438806.1	RefSeq	NP_001425735.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell differentiation

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000540800
Coding exons: 8
Length: 232487
Individuals with no LoFs: 125472
Homozygous LoFs: 1
Heterozygous LoFs: 211
Defined: 125684
p: 0.000844

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.737	393	436	0.901	0.0000340	7861
Missense (PolyPhen)		104	134.36	0.77407		2458
Synonymous	0.724	167	179	0.931	0.0000143	2635
Loss of Function	3.23	6	22.6	0.266	0.00000162	457

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0032	0.0025	notable
Latino/Admixed American	0.00015	0.00012	rare
Ashkenazi Jewish	0.00068	0.00050	rare
East Asian	0.0011	0.00082	notable
Finnish	0.0022	0.0016	notable
European (Non-Finnish)	0.0013	0.00090	notable
South Asian	0.00011	0.000065	rare
Other	0.0020	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Essentials

Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.116

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium