KRTAP12-1

Summary

KRTAP12-1 (keratin associated protein 12-1, HGNC:20529) is a protein-coding gene on chromosome 21q22.3, encoding Keratin-associated protein 12-1 (P59990). 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 353332 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_181686

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20529
Approved symbol	KRTAP12-1
Name	keratin associated protein 12-1
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KRTAP12.1, KAP12.1
Ensembl gene	ENSG00000187175
Ensembl biotype	protein_coding
Entrez	353332

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000391617

RefSeq mRNA: 1 — MANE Select: NM_181686 NM_181686

CCDS: CCDS42966

Canonical transcript exons

ENST00000391617 — 1 exons

Exon	Start	End
ENSE00001382580	44681576	44682163

Expression profiles

Bgee: expression breadth broad, 19 present calls, max score 38.62.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	38.62	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
zone of skin	UBERON:0000014	36.98	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
skin of leg	UBERON:0001511	35.93	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
right lung	UBERON:0002167	30.85	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
heart left ventricle	UBERON:0002084	29.57	silver quality
prefrontal cortex	UBERON:0000451	29.23	gold quality
liver	UBERON:0002107	29.06	gold quality
tonsil	UBERON:0002372	28.78	gold quality
islet of Langerhans	UBERON:0000006	28.64	gold quality
placenta	UBERON:0001987	28.29	gold quality
duodenum	UBERON:0002114	28.14	gold quality
cortex of kidney	UBERON:0001225	28.08	gold quality
urinary bladder	UBERON:0001255	27.85	gold quality
blood	UBERON:0000178	27.71	silver quality
lymph node	UBERON:0000029	27.57	gold quality
leukocyte	CL:0000738	27.12	gold quality
monocyte	CL:0000576	27.08	gold quality
heart	UBERON:0000948	26.51	silver quality
muscle of leg	UBERON:0001383	26.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting KRTAP12-1, 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-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-4522	95.76	66.23	742
HSA-MIR-3130-3P	94.98	66.97	574
HSA-MIR-4793-3P	94.87	65.85	896

Cross-species orthologs

25 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap10-4	ENSMUSG00000069582
mus_musculus	Krtap10-31	ENSMUSG00000071195
mus_musculus	Krtap10-21	ENSMUSG00000094120
mus_musculus	Krtap10-27	ENSMUSG00000094913
mus_musculus	Krtap10-26	ENSMUSG00000095593
mus_musculus	Krtap10-25	ENSMUSG00000095721
mus_musculus	Krtap10-22	ENSMUSG00000095817
mus_musculus	Krtap10-33	ENSMUSG00000095970
mus_musculus	Krtap10-29	ENSMUSG00000096131
mus_musculus	Krtap10-34	ENSMUSG00000096380
mus_musculus	Krtap10-23	ENSMUSG00000096481
mus_musculus	Krtap10-24	ENSMUSG00000111915
mus_musculus	Krtap10-28	ENSMUSG00000112170
mus_musculus	Krtap10-10	ENSMUSG00000112223
mus_musculus	Krtap10-30	ENSMUSG00000112380
mus_musculus	Gm49918	ENSMUSG00000112600
mus_musculus	Krtap10-35	ENSMUSG00000112653
mus_musculus	Krtap10-32	ENSMUSG00000112864
rattus_norvegicus	Krtap10-8l1	ENSRNOG00000001218
rattus_norvegicus	Krtap10-10	ENSRNOG00000032530
rattus_norvegicus	Krtap10-9	ENSRNOG00000043302
rattus_norvegicus	Krtap10-1l1	ENSRNOG00000046538
rattus_norvegicus	Krtap10-1	ENSRNOG00000047532
rattus_norvegicus	LOC120098854	ENSRNOG00000067436
rattus_norvegicus	Krtap10-10l2	ENSRNOG00000069553

Paralogs (47): KRTAP4-4 (ENSG00000171396), KRTAP9-7 (ENSG00000180386), KRTAP5-5 (ENSG00000185940), KRTAP9-8 (ENSG00000187272), KRTAP10-8 (ENSG00000187766), KRTAP10-6 (ENSG00000188155), KRTAP1-1 (ENSG00000188581), KRTAP10-12 (ENSG00000189169), KRTAP4-3 (ENSG00000196156), KRTAP9-9 (ENSG00000198083), KRTAP4-6 (ENSG00000198090), KRTAP4-5 (ENSG00000198271), KRTAP4-1 (ENSG00000198443), KRTAP9-3 (ENSG00000204873), KRTAP4-8 (ENSG00000204880), KRTAP1-4 (ENSG00000204887), KRTAP12-3 (ENSG00000205439), KRTAP10-2 (ENSG00000205445), KRTAP5-6 (ENSG00000205864), KRTAP5-2 (ENSG00000205867), KRTAP16-1 (ENSG00000212657), KRTAP9-6 (ENSG00000212659), KRTAP4-11 (ENSG00000212721), KRTAP4-9 (ENSG00000212722), KRTAP2-3 (ENSG00000212724), KRTAP2-1 (ENSG00000212725), KRTAP10-3 (ENSG00000212935), KRTAP4-12 (ENSG00000213416), KRTAP2-4 (ENSG00000213417), KRTAP2-2 (ENSG00000214518), KRTAP10-4 (ENSG00000215454), KRTAP10-1 (ENSG00000215455), KRTAP10-9 (ENSG00000221837), KRTAP1-5 (ENSG00000221852), KRTAP10-10 (ENSG00000221859), KRTAP12-2 (ENSG00000221864), KRTAP1-3 (ENSG00000221880), KRTAP9-2 (ENSG00000239886), KRTAP9-1 (ENSG00000240542), KRTAP4-7 (ENSG00000240871)

Protein

Protein identifiers

Keratin-associated protein 12-1 — P59990 (reviewed: P59990)

Alternative names: High sulfur keratin-associated protein 12.1, Keratin-associated protein 12.1

All UniProt accessions (1): P59990

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. Restricted to a narrow region of the hair fiber cuticle, lying approximately 20 cell layers above the apex of the dermal papilla of the hair root; not detected in any other tissues.

Similarity. Belongs to the KRTAP type 12 family.

RefSeq proteins (1): NP_859014* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (16 total): repeat 14, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59990-F1	44.70	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: 11 (showing top): chr21q22, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GSE13522_WT_VS_IFNG_KO_SKIN_DN, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MAFG_TARGET_GENES, ZNF224_TARGET_GENES, TATAAA_TATA_01

GO Biological Process (0):

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

GO Cellular Component (3): cytosol (GO:0005829), keratin filament (GO:0045095), 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	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

217 interactions, top by confidence:

A	B	Type	Score
KRTAP12-1	HOXA1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-1	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
HOXA1	KRTAP12-1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	KRTAP12-1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	KRTAP12-1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	KRTAP12-1	psi-mi:“MI:0915”(physical association)	0.720
FHL3	KRTAP12-1	psi-mi:“MI:0915”(physical association)	0.720
TRIP13	KRTAP12-1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-1	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-1	TRIP13	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	KRTAP12-1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-1	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-1	FHL3	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (72): KRTAP12-1 (Two-hybrid), KRTAP12-1 (Two-hybrid), KRTAP12-1 (Two-hybrid), KRTAP12-1 (Two-hybrid), KRTAP12-1 (Two-hybrid), KRTAP12-1 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP12-1 (Two-hybrid), KRTAP12-1 (Two-hybrid), KRTAP12-1 (Two-hybrid)

ESM2 similar proteins: A5A6P5, A6QP35, A8MTY7, A8MVA2, A8MXZ3, O75690, P02438, P02441, P02442, P02443, P08131, P0C7H8, P26371, P59990, P59991, P60014, P60331, P60368, P60369, P60370, P60371, P60372, P60409, P60410, P60411, P60412, P60413, Q05B44, Q07627, Q3V2C1, Q6L8G4, Q6L8G8, Q6L8G9, Q6L8H2, Q701N4, Q8IUG1, Q9BQ66, Q9BYP9, Q9BYQ0, Q9BYQ2

Diamond homologs: P59990, P59991

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 55 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	28	40.0×	8e-40
Formation of the cornified envelope	8	18.0×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	10	61.6×	1e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

176 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44681992:CACGG:C	donor_gain	0.9400
21:44681989:A:T	donor_gain	0.8400
21:44681994:CGG:C	donor_gain	0.8200
21:44682022:CA:C	donor_gain	0.8200
21:44682011:A:AC	donor_gain	0.7800
21:44682012:C:CC	donor_gain	0.7800
21:44681977:T:TA	donor_gain	0.7700
21:44682059:G:A	donor_gain	0.7300
21:44681798:T:C	donor_gain	0.6900
21:44681770:AT:A	donor_gain	0.6800
21:44682013:G:C	donor_gain	0.6700
21:44681992:CA:C	donor_gain	0.6500
21:44682007:G:A	donor_gain	0.6500
21:44682012:CGGG:C	donor_gain	0.6500
21:44681983:G:C	donor_gain	0.6400
21:44681991:A:T	donor_gain	0.6400
21:44681981:A:AC	donor_gain	0.6100
21:44681982:C:CC	donor_gain	0.6100
21:44681643:C:A	donor_gain	0.6000
21:44681962:CA:C	donor_gain	0.5900
21:44681771:T:C	donor_gain	0.5700
21:44681836:G:C	donor_gain	0.5700
21:44681976:AT:A	donor_gain	0.5700
21:44682006:AG:A	donor_gain	0.5600
21:44682019:G:T	donor_gain	0.5600
21:44681738:TGC:T	donor_gain	0.5500
21:44681993:A:C	donor_gain	0.5500
21:44681959:G:T	donor_gain	0.5400
21:44681951:A:AC	donor_gain	0.5300
21:44681952:C:CC	donor_gain	0.5300

AlphaMissense

616 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:44682109:G:C	S5R	0.574
21:44682109:G:T	S5R	0.574
21:44682111:T:G	S5R	0.574

dbSNP variants (sampled 300 via entrez): RS1000844834 (21:44682357 G>C), RS1002451053 (21:44683236 C>A,T), RS1004450692 (21:44683563 G>T), RS1008546938 (21:44682303 T>C), RS1015362864 (21:44683293 G>A), RS1015726595 (21:44683042 G>A), RS1028025404 (21:44683376 C>A), RS1028035218 (21:44683611 A>G), RS1029047678 (21:44682340 A>C,G), RS1031026298 (21:44682677 T>C), RS1031683817 (21:44682361 C>T), RS1033128123 (21:44683949 C>A,G), RS1037283289 (21:44683794 C>T), RS1041350876 (21:44682532 C>G), RS1044791749 (21:44681089 A>C,G)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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