HSD17B4

hydroxysteroid 17-beta dehydrogenase 4, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 5:119452465-119637199

Links

ENSG00000133835 ∙ NCBI:3295 ∙ OMIM:601860 ∙ HGNC:5213 ∙ Uniprot:P51659 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• d-bifunctional protein deficiency (Definitive), mode of inheritance: AR
• Perrault syndrome 1 (Strong), mode of inheritance: AR
• d-bifunctional protein deficiency (Definitive), mode of inheritance: AR
• d-bifunctional protein deficiency (Definitive), mode of inheritance: AR
• Perrault syndrome (Supportive), mode of inheritance: AR
• d-bifunctional protein deficiency (Strong), mode of inheritance: AR
• Perrault syndrome 1 (Strong), mode of inheritance: AR
• d-bifunctional protein deficiency (Definitive), mode of inheritance: AR
• Perrault syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Perrault syndrome 1	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Biochemical; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Obstetric	4061497; 2868085; 2882519; 2921319; 2122104; 1357231; 8147505; 8279468; 9482850; 9915948; 10400999; 11992265; 11743515; 15216544; 16385454; 20673864; 23181892; 24553428
The condition may be clinically recognizable in females, and the exact onset of hearing loss is unclear, but evidence suggests a prelingual onset

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSD17B4 gene.

• Bifunctional peroxisomal enzyme deficiency;Perrault syndrome (24 variants)
• Perrault syndrome;Bifunctional peroxisomal enzyme deficiency (19 variants)
• Bifunctional peroxisomal enzyme deficiency (7 variants)
• Perrault syndrome 1 (4 variants)
• not provided (2 variants)
• Perrault syndrome (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSD17B4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	277	3	283
missense	4	24	216	4	8	256
nonsense	20	14	1			35
start loss		2				2
frameshift	25	57				82
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	58	1	1		62
splice region	1	1	16	81	2	101
non coding			12	276	70	358
Total	51	155	235	558	81

Highest pathogenic variant AF is 0.00000658

Variants in HSD17B4

This is a list of pathogenic ClinVar variants found in the HSD17B4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-119452501-C-A		Bifunctional peroxisomal enzyme deficiency • Perrault syndrome 1	Uncertain significance (Apr 28, 2017)
5-119452501-C-G		Bifunctional peroxisomal enzyme deficiency • Perrault syndrome 1	Benign (Jul 10, 2021)
5-119452548-C-T		Bifunctional peroxisomal enzyme deficiency • Perrault syndrome 1	Benign/Likely benign (Jun 08, 2018)
5-119452549-G-C		Perrault syndrome 1 • Bifunctional peroxisomal enzyme deficiency	Benign/Likely benign (Dec 17, 2018)
5-119452548-C-CGT		HSD17B4-related disorder	Likely benign (Mar 26, 2024)
5-119452556-T-C		HSD17B4-related disorder	Likely benign (Mar 17, 2023)
5-119452559-C-T		not specified	Likely benign (Sep 07, 2017)
5-119452560-G-T			Likely benign (Jul 31, 2020)
5-119452576-A-C		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome	Likely pathogenic (Feb 13, 2019)
5-119452578-G-A		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome 1	Likely pathogenic (Mar 18, 2016)
5-119452581-C-G		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome	Likely benign (Sep 10, 2023)
5-119452581-C-T		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome	Likely benign (Jul 11, 2019)
5-119452586-C-G		not specified • Bifunctional peroxisomal enzyme deficiency • Bifunctional peroxisomal enzyme deficiency;Perrault syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 03, 2024)
5-119452587-G-A		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome	Likely benign (Nov 28, 2023)
5-119452587-G-T		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome	Likely benign (Dec 07, 2020)
5-119452588-C-T		Perrault syndrome;Bifunctional peroxisomal enzyme deficiency	Likely benign (Nov 26, 2021)
5-119452590-G-A		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome	Conflicting classifications of pathogenicity (Dec 20, 2023)
5-119452596-C-G		Perrault syndrome 1	Uncertain significance (Mar 26, 2024)
5-119452596-C-T		Perrault syndrome;Bifunctional peroxisomal enzyme deficiency	Likely benign (Jun 11, 2023)
5-119452597-GACGGGCGGGTGGTACTGGTC-G		Bifunctional peroxisomal enzyme deficiency	Likely pathogenic (Jan 15, 2023)
5-119452602-G-A		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome	Conflicting classifications of pathogenicity (Nov 01, 2023)
5-119452603-C-CG		Bifunctional peroxisomal enzyme deficiency	Pathogenic (Feb 02, 2022)
5-119452605-G-A		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome	Likely benign (Aug 21, 2022)
5-119452608-G-T		Bifunctional peroxisomal enzyme deficiency;Perrault syndrome	Likely benign (Aug 23, 2023)
5-119452612-C-A			Uncertain significance (Feb 22, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSD17B4	protein_coding	protein_coding	ENST00000504811	25	184757

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.42e-10	0.999	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.275	426	410	1.04	0.0000209	4954
Missense in Polyphen		106	134.69	0.78699		1640
Synonymous	-0.977	149	135	1.11	0.00000670	1453
Loss of Function	2.91	23	43.8	0.526	0.00000186	591

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000598	0.000597
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000229	0.000220
Middle Eastern	0.0000544	0.0000544
South Asian	0.000294	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Bifunctional enzyme acting on the peroxisomal beta- oxidation pathway for fatty acids. Catalyzes the formation of 3- ketoacyl-CoA intermediates from both straight-chain and 2-methyl- branched-chain fatty acids. {ECO:0000269|PubMed:8902629, ECO:0000269|PubMed:9089413}.
• Disease: DISEASE: Perrault syndrome 1 (PRLTS1) [MIM:233400]: A sex- influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild mental retardation and cerebellar and peripheral nervous system involvement. {ECO:0000269|PubMed:20673864}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Peroxisome - Homo sapiens (human);Primary bile acid biosynthesis - Homo sapiens (human);27-Hydroxylase Deficiency;Bile Acid Biosynthesis;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;Androgen Receptor Network in Prostate Cancer;Steatosis AOP;Steroid Biosynthesis;mechanism of gene regulation by peroxisome proliferators via ppara;Metabolism of lipids;alpha-linolenic acid (ALA) metabolism;Metabolism of proteins;alpha-linolenic (omega3) and linoleic (omega6) acid metabolism;Tyrosine metabolism;3-oxo-10R-octadecatrienoate beta-oxidation;Leukotriene metabolism;Beta-oxidation of pristanoyl-CoA;Omega-3 fatty acid metabolism;Saturated fatty acids beta-oxidation;Trihydroxycoprostanoyl-CoA beta-oxidation;Beta-oxidation of very long chain fatty acids;Peroxisomal lipid metabolism;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Peroxisomal protein import;Fatty acid metabolism;Metabolism of steroids;Mono-unsaturated fatty acid beta-oxidation;Omega-6 fatty acid metabolism;Valine, leucine and isoleucine degradation;Dimethyl-branched-chain fatty acid mitochondrial beta-oxidation;Di-unsaturated fatty acid beta-oxidation;Phytanic acid peroxisomal oxidation;Vitamin E metabolism;fatty acid β-oxidation (peroxisome);TYSND1 cleaves peroxisomal proteins (Consensus)

Recessive Scores

• pRec: 0.497

Intolerance Scores

• loftool: 0.233
• rvis_EVS: 0.27
• rvis_percentile_EVS: 70.69

Haploinsufficiency Scores

• pHI: 0.660
• hipred: N
• hipred_score: 0.314
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.853

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Hsd17b4
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; hematopoietic system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: hsd17b4
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: very long-chain fatty acid metabolic process;osteoblast differentiation;protein targeting to peroxisome;fatty acid beta-oxidation;bile acid biosynthetic process;androgen metabolic process;estrogen metabolic process;fatty acid beta-oxidation using acyl-CoA oxidase;alpha-linolenic acid metabolic process;very long-chain fatty-acyl-CoA metabolic process;medium-chain fatty-acyl-CoA metabolic process;Sertoli cell development
• Cellular component: peroxisome;peroxisomal membrane;peroxisomal matrix;cytosol;membrane
• Molecular function: 3-hydroxyacyl-CoA dehydrogenase activity;signaling receptor binding;long-chain-enoyl-CoA hydratase activity;isomerase activity;3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity;protein homodimerization activity;17-beta-hydroxysteroid dehydrogenase (NAD+) activity