HHIP

hedgehog interacting protein

Basic information

Region (hg38): 4:144646156-144745271

Links

ENSG00000164161 ∙ NCBI:64399 ∙ OMIM:606178 ∙ HGNC:14866 ∙ Uniprot:Q96QV1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HHIP 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						0
missense			28	1	1	30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	28	1	2

Variants in HHIP

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

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

Position	Type	Phenotype	Significance	ClinVar
4-144646814-C-G		not specified	Uncertain significance (Mar 23, 2022)
4-144646832-A-T		not specified	Uncertain significance (Apr 05, 2023)
4-144646851-T-C		not specified	Uncertain significance (Dec 20, 2023)
4-144652690-T-G		not specified	Uncertain significance (May 04, 2022)
4-144652720-A-G		not specified	Uncertain significance (May 25, 2022)
4-144652753-A-C		not specified	Uncertain significance (Jun 05, 2024)
4-144652792-T-C		not specified	Uncertain significance (Jul 26, 2021)
4-144658735-G-A		HHIP-related condition	Likely benign (May 08, 2024)
4-144658790-G-T		not specified	Uncertain significance (Feb 23, 2023)
4-144658801-A-G		not specified	Uncertain significance (May 08, 2024)
4-144658907-A-G		not specified	Uncertain significance (Dec 12, 2023)
4-144659695-G-A		not specified	Uncertain significance (Aug 13, 2021)
4-144659714-G-A			Benign (Dec 31, 2019)
4-144659729-G-A		not specified	Uncertain significance (Oct 05, 2023)
4-144659771-C-A		not specified	Uncertain significance (Sep 01, 2021)
4-144659771-C-T		not specified	Uncertain significance (Dec 27, 2022)
4-144659774-C-A		not specified	Uncertain significance (Jul 19, 2023)
4-144706588-G-A		not specified	Uncertain significance (Dec 05, 2022)
4-144706672-A-G		not specified	Uncertain significance (Jan 26, 2023)
4-144711961-A-C		not specified	Uncertain significance (Nov 17, 2023)
4-144711988-A-G		not specified	Uncertain significance (May 18, 2022)
4-144711994-C-T			Likely benign (Apr 23, 2018)
4-144714290-T-C		not specified	Uncertain significance (Mar 12, 2024)
4-144714329-G-A		not specified	Uncertain significance (May 25, 2022)
4-144714358-C-G			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HHIP	protein_coding	protein_coding	ENST00000296575	13	99251

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.954	0.0456	125740	0	7	125747	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.36	302	376	0.802	0.0000188	4587
Missense in Polyphen		68	99.846	0.68105		1123
Synonymous	-0.765	156	144	1.08	0.00000757	1337
Loss of Function	4.40	5	31.7	0.158	0.00000146	431

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family. {ECO:0000269|PubMed:11472839, ECO:0000269|PubMed:19561609}.
• Pathway: Basal cell carcinoma - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);HH-Ncore;Hedgehog ,on, state;Hedgehog Signaling Pathway;Signal Transduction;Hedgehog;Hedgehog;Ligand-receptor interactions;GLI proteins bind promoters of Hh responsive genes to promote transcription;Hedgehog ,on, state;Signaling by Hedgehog;Signaling events mediated by the Hedgehog family (Consensus)

Recessive Scores

• pRec: 0.132

Intolerance Scores

• loftool: 0.361
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.76

Haploinsufficiency Scores

• pHI: 0.229
• hipred: Y
• hipred_score: 0.737
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.820

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hhip
• Phenotype: immune system phenotype; digestive/alimentary 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); vision/eye phenotype; hematopoietic 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); embryo phenotype; respiratory system phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: hhip
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: smoothened signaling pathway;neuroblast proliferation;dorsal/ventral pattern formation;negative regulation of signal transduction;regulation of fibroblast growth factor receptor signaling pathway;negative regulation of apoptotic process;negative regulation of smoothened signaling pathway;skeletal system morphogenesis;epithelial tube branching involved in lung morphogenesis
• Cellular component: extracellular region;nucleus;cytoplasm;integral component of plasma membrane;cell surface;ciliary membrane
• Molecular function: catalytic activity;protein binding;zinc ion binding;hedgehog family protein binding