HHAT

hedgehog acyltransferase, the group of Membrane bound O-acyltransferase family

Basic information

Region (hg38): 1:210328251-210676296

Links

ENSG00000054392 ∙ NCBI:55733 ∙ OMIM:605743 ∙ HGNC:18270 ∙ Uniprot:Q5VTY9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• chondrodysplasia-pseudohermaphroditism syndrome (Moderate), mode of inheritance: AR
• chondrodysplasia-pseudohermaphroditism syndrome (Supportive), mode of inheritance: AR
• chondrodysplasia-pseudohermaphroditism syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nivelon-Nivelon-Mabille syndrome	AR	General	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	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	1342874; 24784881; 30912300

ClinVar

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

• not provided (51 variants)
• Inborn genetic diseases (20 variants)
• Chondrodysplasia-pseudohermaphroditism syndrome (2 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HHAT 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			1	10	7	18
missense			25	6	5	36
nonsense	1					1
start loss		1	1			2
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				4	2	6
non coding			4	3	2	9
Total	1	1	32	19	14

Highest pathogenic variant AF is 0.00000657

Variants in HHAT

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

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

Position	Type	Phenotype	Significance	ClinVar
1-210329039-G-C		not specified	Uncertain significance (Nov 07, 2022)
1-210329051-G-A		not specified	Uncertain significance (Mar 07, 2024)
1-210329071-C-G		not specified	Uncertain significance (Mar 02, 2023)
1-210329091-G-C		HHAT-related disorder	Likely benign (Jun 27, 2019)
1-210348976-A-T		Inborn genetic diseases	Likely pathogenic (Jun 16, 2017)
1-210348978-G-A			Uncertain significance (Oct 14, 2020)
1-210349026-C-T			Likely benign (Sep 10, 2023)
1-210349043-A-G		HHAT-related disorder	Likely benign (Nov 28, 2022)
1-210349086-A-G			Likely benign (Dec 02, 2021)
1-210362834-C-CT			Benign (Aug 09, 2021)
1-210362846-G-T			Likely benign (Jan 19, 2018)
1-210362847-G-T			Likely benign (Jan 19, 2018)
1-210362905-G-A			Uncertain significance (Aug 10, 2022)
1-210362924-A-C			Likely benign (Nov 27, 2023)
1-210362934-C-A			Benign (Jan 24, 2024)
1-210387472-C-T		not specified	Uncertain significance (Nov 08, 2022)
1-210387473-G-A			Likely benign (Dec 31, 2019)
1-210387475-C-A		not specified	Uncertain significance (Jan 26, 2022)
1-210387476-C-T			Likely benign (Mar 04, 2022)
1-210387575-A-G			Benign (Dec 06, 2023)
1-210400529-C-T			Uncertain significance (Jun 16, 2021)
1-210400538-C-A		not specified	Uncertain significance (Feb 23, 2023)
1-210400554-TACC-T		Chondrodysplasia-pseudohermaphroditism syndrome	Uncertain significance (Sep 21, 2020)
1-210400580-A-G		not specified	Uncertain significance (Aug 07, 2023)
1-210400585-C-T		not specified	Uncertain significance (Dec 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HHAT	protein_coding	protein_coding	ENST00000545154	11	348043

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.25e-8	0.983	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0546	272	275	0.991	0.0000154	3161
Missense in Polyphen		102	97.336	1.0479		1140
Synonymous	0.941	105	118	0.890	0.00000730	989
Loss of Function	2.26	17	30.4	0.558	0.00000146	315

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000449	0.000449
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.000327	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000327	0.000326
South Asian	0.000426	0.000425
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes N-terminal palmitoylation of SHH; which is required for SHH signaling. May bind GTP. {ECO:0000250, ECO:0000269|PubMed:11486055}.
• Pathway: HH-Ncore;Signal Transduction;Hedgehog;Hedgehog ligand biogenesis;Signaling by Hedgehog;Signaling events mediated by the Hedgehog family (Consensus)

Intolerance Scores

• loftool: 0.961
• rvis_EVS: -0.02
• rvis_percentile_EVS: 52.25

Haploinsufficiency Scores

• pHI: 0.101
• hipred: N
• hipred_score: 0.414
• ghis: 0.478

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.946

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hhat
• Phenotype: skeleton phenotype; limbs/digits/tail 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; vision/eye 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); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; respiratory system phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: smoothened signaling pathway;multicellular organism development;protein palmitoylation
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: GTP binding;O-acyltransferase activity;palmitoyltransferase activity