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

uncombable hair syndrome 3 (Limited), mode of inheritance: AR

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.

not_specified (395 variants)
not_provided (27 variants)
Uncombable_hair_syndrome_3 (5 variants)

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. These statistics are base on transcript: NM_000007113.4. 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				16 clinvar	1 clinvar	17
missense			375 clinvar	24 clinvar	3 clinvar	402
nonsense		1 clinvar				1
start loss				1		1
frameshift		2 clinvar	2 clinvar	1 clinvar		5
splice donor/acceptor (+/-2bp)						0
Total	0	3	377	42	4

Highest pathogenic variant AF is 0.0003795474

Loading clinvar variants...

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
ghis

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
Phenotype

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