TCHH

trichohyalin, the group of S100 fused type protein family|EF-hand domain containing

Basic information

Region (hg38): 1:152106317-152115444

Previous symbols: [ "THH" ]

Links

ENSG00000159450 ∙ NCBI:7062 ∙ OMIM:190370 ∙ HGNC:11791 ∙ Uniprot:Q07283 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Uncombable hair syndrome 3	AR	General	The clinical relevance of the condition is unclear	Dermatologic	27866708

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCHH 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				13	2	15
missense			171	11	4	186
nonsense		1				1
start loss				1		1
frameshift		1				1
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	2	171	25	7

Variants in TCHH

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

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

Position	Type	Phenotype	Significance	ClinVar
1-152107392-C-A		not specified	Uncertain significance (Oct 13, 2023)
1-152107430-A-G			Likely benign (Oct 17, 2017)
1-152107435-T-G		not specified	Uncertain significance (Mar 04, 2024)
1-152107453-T-C		not specified	Uncertain significance (Oct 13, 2023)
1-152107465-G-A		not specified	Uncertain significance (Aug 02, 2021)
1-152107532-G-T		not specified	Uncertain significance (Feb 16, 2023)
1-152107535-C-G		not specified	Uncertain significance (Mar 31, 2023)
1-152107565-G-C		not specified	Likely benign (Apr 19, 2024)
1-152107581-T-G		not specified	Uncertain significance (Jun 22, 2024)
1-152107612-C-T		not specified	Uncertain significance (Nov 18, 2022)
1-152107645-G-C		not specified	Uncertain significance (Nov 21, 2022)
1-152107681-G-A		not specified	Uncertain significance (Jul 19, 2023)
1-152107731-T-C		not specified	Uncertain significance (Jun 16, 2024)
1-152107762-C-T		not specified	Likely benign (Feb 27, 2024)
1-152107765-C-G		not specified	Uncertain significance (Sep 01, 2021)
1-152107795-C-T		not specified	Uncertain significance (Feb 27, 2024)
1-152107819-C-T		not specified	Uncertain significance (Apr 08, 2024)
1-152107869-C-G		not specified	Uncertain significance (Dec 05, 2022)
1-152107877-G-C			Likely benign (Aug 01, 2022)
1-152107884-T-C		not specified	Uncertain significance (Mar 04, 2024)
1-152107948-G-A		not specified	Uncertain significance (Feb 14, 2023)
1-152107992-C-T		not specified	Uncertain significance (Dec 07, 2021)
1-152108034-T-G		not specified	Uncertain significance (Mar 24, 2023)
1-152108109-T-C		not specified	Uncertain significance (Oct 26, 2021)
1-152108112-C-G		not specified	Uncertain significance (Aug 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCHH	protein_coding	protein_coding	ENST00000368804	2	7764

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.71e-24	0.114	124070	3	744	124817	0.00300

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-6.60	1509	940	1.61	0.0000581	12680
Missense in Polyphen		3	2.1152	1.4183		19
Synonymous	-5.26	543	408	1.33	0.0000208	3404
Loss of Function	1.68	44	57.7	0.762	0.00000277	619

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00376	0.00367
Ashkenazi Jewish	0.000356	0.000298
East Asian	0.00124	0.00117
Finnish	0.00165	0.00153
European (Non-Finnish)	0.00562	0.00501
Middle Eastern	0.00124	0.00117
South Asian	0.000947	0.000915
Other	0.00226	0.00198

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Intermediate filament-associated protein that associates in regular arrays with keratin intermediate filaments (KIF) of the inner root sheath cells of the hair follicle and the granular layer of the epidermis. It later becomes cross-linked to KIF by isodipeptide bonds. It may serve as scaffold protein, together with involucrin, in the organization of the cell envelope or even anchor the cell envelope to the KIF network. It may be involved in its own calcium-dependent postsynthetic processing during terminal differentiation.
• Disease: DISEASE: Uncombable hair syndrome 3 (UHS3) [MIM:617252]: A form of uncombable hair syndrome, a condition characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair. Most individuals are affected early in childhood and the hair takes on a spun-glass appearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. The hair growth rate can range from slow to normal, and the condition improves with age. {ECO:0000269|PubMed:27866708}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Keratinization;Developmental Biology;Formation of the cornified envelope (Consensus)

Intolerance Scores

• loftool: 0.983
• rvis_EVS: 1.54
• rvis_percentile_EVS: 95.58

Haploinsufficiency Scores

• pHI: 0.159
• hipred: Y
• hipred_score: 0.516

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.663

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tchh

Gene ontology

• Biological process: biological_process;intermediate filament organization;cornification
• Cellular component: cornified envelope;cytosol;cytoskeleton
• Molecular function: calcium ion binding;transition metal ion binding