KRTAP8-1

Summary

KRTAP8-1 (keratin associated protein 8-1, HGNC:18935) is a protein-coding gene on chromosome 21q22.11, encoding Keratin-associated protein 8-1 (Q8IUC2). In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-link….

Predicted to be located in cytosol.

Source: NCBI Gene 337879 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 11 total
• MANE Select transcript: NM_175857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18935
Approved symbol	KRTAP8-1
Name	keratin associated protein 8-1
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	KAP8.1
Ensembl gene	ENSG00000183640
Ensembl biotype	protein_coding
Entrez	337879

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000329621

RefSeq mRNA: 1 — MANE Select: NM_175857 NM_175857

CCDS: CCDS13607

Canonical transcript exons

ENST00000329621 — 1 exons

Exon	Start	End
ENSE00001315685	30812697	30813274

Expression profiles

Bgee: expression breadth broad, 55 present calls, max score 62.39.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0733 / max 97.2090, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190129	0.0733	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	62.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.43	gold quality
parotid gland	UBERON:0001831	52.34	gold quality
right lung	UBERON:0002167	50.39	gold quality
heart right ventricle	UBERON:0002080	49.60	gold quality
buccal mucosa cell	CL:0002336	46.76	gold quality
skin of hip	UBERON:0001554	44.50	silver quality
nipple	UBERON:0002030	44.24	gold quality
amniotic fluid	UBERON:0000173	44.02	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
penis	UBERON:0000989	43.34	silver quality
secondary oocyte	CL:0000655	42.57	gold quality
colonic epithelium	UBERON:0000397	42.15	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality
mammary duct	UBERON:0001765	39.98	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting KRTAP8-1, 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-4283	100.00	66.42	2097
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-125B-2-3P	96.69	68.38	1210
HSA-MIR-6847-3P	96.50	67.30	582
HSA-MIR-3169	96.40	67.58	698
HSA-MIR-4740-5P	96.25	67.96	726

Literature-anchored findings (GeneRIF, showing 1)

• The helical arrangement of intermediate filament proteins found in the orthocortex, which is uniquely distributed on the convex fiber side of the hair, is regulated by KAP8.1 (PMID:23791804)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap8-1	ENSMUSG00000059632
rattus_norvegicus	Krtap8-1	ENSRNOG00000082217

Protein

Protein identifiers

Keratin-associated protein 8-1 — Q8IUC2 (reviewed: Q8IUC2)

Alternative names: High glycine-tyrosine keratin-associated protein 8.1

All UniProt accessions (1): Q8IUC2

UniProt curated annotations — full annotation on UniProt →

Function. In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.

Subunit / interactions. Interacts with hair keratins.

Tissue specificity. Is essentially restricted to only one vertical half of the hair forming compartment and in beard hairs is absent from the central medulla.

Similarity. Belongs to the KRTAP type 8 family.

RefSeq proteins (1): NP_787053* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021743	KRTAP_type8/19/20/21/22	Family
IPR039351	KRTAP8-1	Family

Pfam: PF11759

UniProt features (2 total): chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUC2-F1	40.84	0.00

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 65 (showing top): MARTINEZ_RB1_TARGETS_DN, OCT1_06, chr21q22, ISRE_01, TAATTA_CHX10_01, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, AR_Q6, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, WNT_UP.V1_UP, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, EBNA1BP2_TARGET_GENES, AAANWWTGC_UNKNOWN, MIR4653_5P

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), intermediate filament (GO:0005882)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP8-1	KRTAP7-1	Q8IUC3	821
KRTAP8-1	KRTAP24-1	Q3LI83	803
KRTAP8-1	KRTAP11-1	Q8IUC1	771
KRTAP8-1	KRTAP20-2	Q3LI61	767
KRTAP8-1	KRTAP6-1	Q3LI64	767
KRTAP8-1	KRTAP6-2	Q3LI66	765
KRTAP8-1	KRTAP22-1	Q3MIV0	765
KRTAP8-1	KRTAP20-1	Q3LI63	761
KRTAP8-1	KRTAP15-1	Q3LI76	760
KRTAP8-1	KRTAP13-3	Q3SY46	753
KRTAP8-1	KRTAP13-1	Q8IUC0	746
KRTAP8-1	KRTAP6-3	Q3LI67	724
KRTAP8-1	SCYGR1	A0A286YEY9	720
KRTAP8-1	KRTAP26-1	Q6PEX3	670
KRTAP8-1	KRTAP21-3	Q3LHN1	663

IntAct

324 interactions, top by confidence:

A	B	Type	Score
DAZAP2	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP8-1	DAZAP2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP8-1	DAB1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP8-1	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP8-1	RBPMS	psi-mi:“MI:0915”(physical association)	0.560
KRTAP8-1	HEL-S-101	psi-mi:“MI:0915”(physical association)	0.560
DAB1	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
RBPMS	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
HEL-S-101	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
ZC3H10	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
POU6F2	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
YTHDF1	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
TLE5	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
PLSCR4	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
ARID5A	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP8-1	CAMK2A	psi-mi:“MI:0915”(physical association)	0.560
FAM83A	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
RBPMS2	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (80): KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP8-1 (Two-hybrid)

ESM2 similar proteins: A8HSH8, A8Y3N1, B6JB57, C0H3Q7, C0H3V0, C0H3V1, C0H3Y2, C0H3Y8, C0H409, C0H435, H2A0M6, I2HB52, L8EBJ6, O08633, O31793, O31861, O31888, O34654, O44662, O44663, O44664, O44665, O52055, O52179, P05687, P05688, P08175, P08825, P08826, P08827, P0C0U2, P0C0U3, P0CI94, P0CI95, P34407, P34625, P43513, P43514, P43516, P43517

Diamond homologs: O08633, P02448, Q8IUC2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

194 predictions. Top by Δscore:

Variant	Effect	Δscore
21:30813178:AGCAT:A	donor_gain	0.9000
21:30813167:G:C	donor_gain	0.8600
21:30813182:T:TA	donor_gain	0.8200
21:30813055:T:TA	donor_gain	0.7800
21:30813108:A:AC	donor_gain	0.7800
21:30813109:C:CC	donor_gain	0.7800
21:30813166:AGCTG:A	donor_gain	0.7700
21:30813052:ATCT:A	donor_gain	0.7600
21:30813091:AG:A	donor_gain	0.7200
21:30813103:AGC:A	donor_gain	0.7200
21:30813062:G:C	donor_gain	0.7100
21:30813053:T:C	donor_gain	0.7000
21:30813103:AG:A	donor_gain	0.7000
21:30813061:AG:A	donor_gain	0.6900
21:30813130:AG:A	donor_gain	0.6600
21:30813092:G:C	donor_gain	0.6500
21:30812882:C:A	donor_gain	0.6400
21:30813131:G:C	donor_gain	0.6400
21:30813104:G:C	donor_gain	0.6300
21:30813181:AT:A	donor_gain	0.6100
21:30813110:T:C	donor_gain	0.6000
21:30813170:G:GA	donor_gain	0.6000
21:30813196:C:A	donor_gain	0.5900
21:30812699:CCAG:C	donor_gain	0.5800
21:30812886:GGGAC:G	acceptor_gain	0.5800
21:30812811:T:TA	donor_gain	0.5700
21:30812888:GACTC:G	acceptor_gain	0.5700
21:30813085:AG:A	donor_gain	0.5700
21:30813106:C:T	donor_gain	0.5700
21:30812877:T:A	donor_gain	0.5600

AlphaMissense

396 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:30813143:G:C	S26R	0.972
21:30813143:G:T	S26R	0.972
21:30813145:T:G	S26R	0.972
21:30813139:C:G	G28R	0.920
21:30813138:C:T	G28D	0.916
21:30813132:C:T	G30D	0.914
21:30813122:G:C	S33R	0.910
21:30813122:G:T	S33R	0.910
21:30813124:T:G	S33R	0.910
21:30813099:C:T	G41D	0.899
21:30813105:C:T	G39D	0.897
21:30813106:C:G	G39R	0.896
21:30813087:C:T	G45D	0.885
21:30813133:C:G	G30R	0.883
21:30813148:A:C	Y25D	0.879
21:30813151:C:G	G24R	0.874
21:30813151:C:T	G24R	0.874
21:30813100:C:G	G41R	0.869
21:30813148:A:G	Y25H	0.868
21:30813150:C:T	G24E	0.864
21:30813144:C:T	S26N	0.848
21:30813126:C:T	G32D	0.847
21:30813088:C:G	G45R	0.843
21:30813093:C:T	G43D	0.837
21:30813172:C:G	G17R	0.837
21:30813144:C:A	S26I	0.836
21:30813138:C:A	G28V	0.835
21:30813132:C:A	G30V	0.827
21:30813167:G:C	S18R	0.825
21:30813167:G:T	S18R	0.825

dbSNP variants (sampled 300 via entrez): RS1000247904 (21:30812611 A>G), RS1000701615 (21:30812853 G>A,C), RS1001106069 (21:30813745 C>T), RS1001656310 (21:30814305 G>A), RS1005254324 (21:30813331 A>C), RS1008008604 (21:30814902 C>T), RS1009388914 (21:30812865 G>C), RS1010235969 (21:30813284 G>A), RS1010281749 (21:30814090 A>T), RS1011243533 (21:30814849 G>A,C), RS1011732436 (21:30814590 G>A,C), RS1014295235 (21:30812582 T>C), RS1014368801 (21:30812364 G>A), RS1015609071 (21:30812343 G>A), RS1016609393 (21:30813712 A>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003875_25	Gut microbiota (bacterial taxa)	6.000000e-10
GCST003875_26	Gut microbiota (bacterial taxa)	6.000000e-10
GCST010396_1	Gut microbiota (bacterial taxa, hurdle binary method)	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases mutagenesis, decreases methylation	2
avobenzone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Phthalic Acids	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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