HHAT

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

Basic information

Region (hg38): 1:210328252-210676296

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_specified (69 variants)
not_provided (57 variants)
HHAT-related_disorder (10 variants)
Chondrodysplasia-pseudohermaphroditism_syndrome (7 variants)
Inborn_genetic_diseases (1 variants)
See_cases (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. These statistics are base on transcript: NM_000018194.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				17 clinvar	6 clinvar	23
missense	2 clinvar		74 clinvar	12 clinvar	2 clinvar	90
nonsense	1 clinvar	1 clinvar				2
start loss		1	1			2
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	3	2	75	29	8

Highest pathogenic variant AF is 0.0000131392

Loading clinvar variants...

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