HSDL2

protein-coding

hydroxysteroid dehydrogenase like 2, the group of Short chain dehydrogenase/reductase superfamily

Gene summary

Predicted to enable oxidoreductase activity. Involved in cholesterol homeostasis. Located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C9orf99

MANE transcript

NM_032303.5

Inheritance

—

ClinVar variants

U:39B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr9:112,380,080-112,472,405

External References & Databases

Ensembl (ENSG00000119471)

Transcript & Mutation Effects

hg38 • Region Span ~92.3 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 HSDL2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032303.5. 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					1 clinvar	1
missense			35 clinvar	5 clinvar	1 clinvar	41
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	39	5	2	46

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032303.5	RefSeq	NP_115679.2	11	MANE Select
ENST00000398805.8	Ensembl	ENSP00000381785.3	11	MANE Select
NM_001195822.2	RefSeq	NP_001182751.1	9	Standard
ENST00000398803.1	Ensembl	ENSP00000381783.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process
oxidation-reduction process

Molecular Function

molecular_function
oxidoreductase activity

Cellular Component

mitochondrion
peroxisome
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398805
Coding exons: 11
Length: 92474
Individuals with no LoFs: 124726
Homozygous LoFs: 1
Heterozygous LoFs: 66
Defined: 124793
p: 0.000268

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.904	182	220	0.828	0.0000103	2760
Missense (PolyPhen)		70	93.158	0.75141		1138
Synonymous	0.672	67	74.4	0.901	0.00000371	770
Loss of Function	1.96	10	19.3	0.518	9.05e-7	262

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.00039	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.0010	0.00095	notable
Other	0.00067	0.00066	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has apparently no steroid dehydrogenase activity. {ECO:0000269|PubMed:19703561}.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.474
RVIS EVS: 0.02
RVIS percentile EVS: 55.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.332

Gene Damage Prediction

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