TCHHL1

Summary

TCHHL1 (trichohyalin like 1, HGNC:31796) is a protein-coding gene on chromosome 1q21.3, encoding Trichohyalin-like protein 1 (Q5QJ38).

This gene belongs to the S100 fused-type protein (SFTP) gene family, and is located in a cluster of SFTP genes on chromosome 1q21. Several members of this family have been implicated in the development of complex skin disorders. This gene is evolutionarily conserved; its expression appears to be hair-specific and spatially restricted within the distal inner root sheath of the hair follicle. It thus may have an important role in hair morphogenesis.

Source: NCBI Gene 126637 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 119 total
• MANE Select transcript: NM_001008536

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31796
Approved symbol	TCHHL1
Name	trichohyalin like 1
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182898
Ensembl biotype	protein_coding
Entrez	126637

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368806

RefSeq mRNA: 1 — MANE Select: NM_001008536 NM_001008536

CCDS: CCDS30857

Canonical transcript exons

ENST00000368806 — 3 exons

Exon	Start	End
ENSE00001447995	152084141	152087543
ENSE00001447996	152088006	152088163
ENSE00001447997	152089020	152089064

Expression profiles

Bgee: expression breadth tissue_specific, 4 present calls, max score 43.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0197 / max 14.5182, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14527	0.0197	5

Top tissues by expression

131 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	43.89	gold quality
bone marrow cell	CL:0002092	42.41	gold quality
colonic epithelium	UBERON:0000397	41.36	gold quality
lower esophagus mucosa	UBERON:0035834	41.01	silver quality
placenta	UBERON:0001987	38.58	gold quality
skeletal muscle tissue	UBERON:0001134	37.57	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.34	gold quality
bone marrow	UBERON:0002371	34.94	gold quality
muscle tissue	UBERON:0002385	34.14	gold quality
tonsil	UBERON:0002372	31.63	gold quality
monocyte	CL:0000576	31.11	gold quality
leukocyte	CL:0000738	30.79	gold quality
calcaneal tendon	UBERON:0003701	29.98	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.62	gold quality
ectocervix	UBERON:0012249	29.19	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
uterine cervix	UBERON:0000002	28.46	gold quality
duodenum	UBERON:0002114	28.14	gold quality
islet of Langerhans	UBERON:0000006	27.88	gold quality
lymph node	UBERON:0000029	27.57	gold quality
blood	UBERON:0000178	27.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.31	gold quality
right coronary artery	UBERON:0001625	26.79	gold quality
skin of abdomen	UBERON:0001416	26.61	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting TCHHL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-6731-5P	99.28	67.42	2375

Literature-anchored findings (GeneRIF, showing 3)

• We identified and characterized a novel S100 fused type protein expressed in hair follicles (PMID:21614011)
• These findings highlight the possibility that TCHHL1 proteins are expressed in growing keratinocytes of the epidermis and might be associated with the proliferation of keratinocytes. (PMID:23376073)
• Uncommon variants in FLG2 and TCHHL1 are associated with remission of atopic dermatitis in a large longitudinal US cohort. (PMID:34984527)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tchhl1	ENSMUSG00000027908
rattus_norvegicus	Tchhl1	ENSRNOG00000009610
drosophila_melanogaster	Cp190	FBGN0000283
drosophila_melanogaster	CG9915	FBGN0030738
drosophila_melanogaster	CG12592	FBGN0037811
caenorhabditis_elegans		WBGENE00008729

Paralogs (3): SAMD15 (ENSG00000100583), MDN1 (ENSG00000112159), IWS1 (ENSG00000163166)

Protein

Protein identifiers

Trichohyalin-like protein 1 — Q5QJ38 (reviewed: Q5QJ38)

Alternative names: Basalin, Protein S100-A17, S100 calcium-binding protein A17

All UniProt accessions (1): Q5QJ38

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the S-100 family.

RefSeq proteins (1): NP_001008536* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013787	S100_Ca-bd_sub	Domain
IPR034325	S-100_dom	Domain
IPR042937	TCHHL1	Family

Pfam: PF01023

UniProt features (19 total): compositionally biased region 14, region of interest 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5QJ38-F1	42.28	0.02

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): DARWICHE_PAPILLOMA_PROGRESSION_RISK, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, chr1q21, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR944, MIR6833_3P, MIR4533, MIR4768_5P, MIR6077, MIR8085, MIR6731_5P, MIR6715A_3P, MIR3177_5P, MIR93_3P, MIR6804_5P

GO Biological Process (0):

GO Molecular Function (1): transition metal ion binding (GO:0046914)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	1

Protein interactions and networks

STRING

1155 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCHHL1	SPRR4	Q96PI1	626
TCHHL1	S100A3	P33764	626
TCHHL1	LELP1	Q5T871	601
TCHHL1	S100A11	P31949	572
TCHHL1	S100A2	P29034	572
TCHHL1	S100A7L2	Q5SY68	528
TCHHL1	CRNN	Q9UBG3	512
TCHHL1	LCE3C	Q5T5A8	499
TCHHL1	KPRP	Q5T749	484
TCHHL1	FLG	P20930	471
TCHHL1	KRT81	Q14533	457
TCHHL1	RPF2	Q9H7B2	455
TCHHL1	S100Z	Q8WXG8	450
TCHHL1	S100A4	P26447	446
TCHHL1	SPRR3	Q9UBC9	445

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TCHHL1	PFN3	psi-mi:“MI:0914”(association)	0.350
PPP4C	MID1	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): PFN3 (Affinity Capture-MS), SLC9A3R2 (Affinity Capture-MS), TCHHL1 (Affinity Capture-MS), TCHHL1 (Affinity Capture-MS), TCHHL1 (Cross-Linking-MS (XL-MS)), TCHHL1 (Co-fractionation)

ESM2 similar proteins: A0A1B0GTH6, A0A1B0GUW6, A0A1D5RMD1, A2AQH4, A4FU49, A6NJ88, C4P6S0, D3YU32, E9PAV3, F1QU13, I3L273, J3KML8, P70670, Q32L62, Q3V0E1, Q3V3Q4, Q4R729, Q5H9F3, Q5QJ38, Q5SWP3, Q5U4C1, Q5VWK0, Q5VYM1, Q68DN1, Q6AZ54, Q7TSG5, Q810T2, Q8CH19, Q8K4E0, Q8N3K9, Q8N5Q1, Q8NDH2, Q8TCU4, Q8WNU4, Q8WWL7, Q920R4, Q921B4, Q923B3, Q96JA4, Q96M34

Diamond homologs: A6QP92, P20930, P37709, P97347, Q07283, Q2VIS4, Q5D862, Q5QJ38, Q6XPR3, Q9D3P1, Q9UBG3, O77691, O77791, P02632, P02633, P02639, P04163, P05943, P05964, P06703, P07091, P08207, P14069, P22793, P23297, P24479, P25815, P27003, P29377, P30801, P31949, P31950, P35467, P56565, P60902, P60903, P62504, P79105, P80310, P80511

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

119 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	12
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

131 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152088000:GCTCA:G	donor_loss	1.0000
1:152088001:CTCA:C	donor_loss	1.0000
1:152088002:TCAC:T	donor_loss	1.0000
1:152088003:CAC:C	donor_loss	1.0000
1:152088004:A:AG	donor_loss	1.0000
1:152088005:CCT:C	donor_loss	1.0000
1:152088161:AGG:A	acceptor_gain	1.0000
1:152088162:GG:G	acceptor_gain	1.0000
1:152088164:C:CC	acceptor_gain	1.0000
1:152087539:CAGGG:C	acceptor_gain	0.9900
1:152088160:GAGG:G	acceptor_gain	0.9900
1:152088162:GGC:G	acceptor_loss	0.9900
1:152088163:GC:G	acceptor_loss	0.9900
1:152088164:C:A	acceptor_loss	0.9900
1:152088166:G:C	acceptor_gain	0.9900
1:152088166:G:GC	acceptor_gain	0.9900
1:152089015:CTTA:C	donor_loss	0.9900
1:152089017:TA:T	donor_loss	0.9900
1:152089018:ACC:A	donor_loss	0.9900
1:152089019:C:G	donor_loss	0.9900
1:152087544:C:CC	acceptor_gain	0.9800
1:152088027:G:A	donor_gain	0.9800
1:152088159:AGAGG:A	acceptor_gain	0.9800
1:152089018:A:AC	donor_gain	0.9800
1:152089019:C:CC	donor_gain	0.9800
1:152089019:CCTA:C	donor_gain	0.9800
1:152089019:CCT:C	donor_gain	0.9700
1:152089019:CCTAG:C	donor_gain	0.9700
1:152089018:AC:A	donor_gain	0.9600
1:152089019:CC:C	donor_gain	0.9600

AlphaMissense

5937 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152088099:G:C	F15L	0.979
1:152088099:G:T	F15L	0.979
1:152088101:A:G	F15L	0.979
1:152087463:A:C	F73L	0.970
1:152087463:A:T	F73L	0.970
1:152087465:A:G	F73L	0.970
1:152088037:A:G	L36P	0.945
1:152087472:A:C	F70L	0.939
1:152087472:A:T	F70L	0.939
1:152087474:A:G	F70L	0.939
1:152088046:A:G	L33P	0.921
1:152088089:C:G	A19P	0.917
1:152088100:A:G	F15S	0.910
1:152087464:A:G	F73S	0.890
1:152087448:G:C	F78L	0.873
1:152087448:G:T	F78L	0.873
1:152087450:A:G	F78L	0.873
1:152088061:A:G	L28P	0.863
1:152087461:A:T	V74D	0.859
1:152088061:A:T	L28Q	0.853
1:152088091:T:G	Y18S	0.850
1:152088100:A:C	F15C	0.843
1:152088037:A:T	L36H	0.842
1:152087464:A:C	F73C	0.840
1:152088112:A:T	V11E	0.839
1:152088088:G:T	A19D	0.838
1:152088092:A:C	Y18D	0.835
1:152088133:A:G	L4P	0.801
1:152087456:C:G	A76P	0.798
1:152088061:A:C	L28R	0.793

dbSNP variants (sampled 300 via entrez): RS1000788166 (1:152089580 G>A,T), RS1000828334 (1:152087027 T>C), RS1000971107 (1:152089352 A>G), RS1001676764 (1:152090551 G>T), RS1001796306 (1:152090476 T>C), RS1001833190 (1:152085006 CCT>C,CCTCT), RS1002625840 (1:152088878 G>A), RS1002678347 (1:152089157 A>G,T), RS1002900797 (1:152084304 A>G), RS1003530140 (1:152084553 T>C), RS1005028127 (1:152087734 C>A,T), RS1005970153 (1:152085639 A>C,G,T), RS1006261349 (1:152088486 G>A), RS1006788403 (1:152089589 GAA>G,GA,GAAA,GAAAA), RS1006813696 (1:152090907 A>C,G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:600057

GenCC curated gene-disease

Mondo (1): bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039)

Orphanet (1): Classic bladder exstrophy (Orphanet:93930)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST005191_11	Hair shape	2.000000e-82
GCST005191_3	Hair shape	2.000000e-152
GCST006661_183	Male-pattern baldness	1.000000e-10
GCST007563_31	Allergic disease (asthma, hay fever or eczema)	2.000000e-08
GCST007563_33	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST007564_24	Asthma or allergic disease (pleiotropy)	5.000000e-12
GCST007798_6	Asthma	2.000000e-20
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25
GCST009798_26	Asthma	2.000000e-21
GCST010984_1	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	2.000000e-15
GCST010985_38	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	2.000000e-47

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Malathion	decreases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.