KRTAP13-3

Summary

KRTAP13-3 (keratin associated protein 13-3, HGNC:18925) is a protein-coding gene on chromosome 21q22.11, encoding Keratin-associated protein 13-3 (Q3SY46). 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 337960 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 26 total — 2 pathogenic
• MANE Select transcript: NM_181622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18925
Approved symbol	KRTAP13-3
Name	keratin associated protein 13-3
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	KAP13.3
Ensembl gene	ENSG00000240432
Ensembl biotype	protein_coding
Entrez	337960

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000390690

RefSeq mRNA: 1 — MANE Select: NM_181622 NM_181622

CCDS: CCDS13591

Canonical transcript exons

ENST00000390690 — 1 exons

Exon	Start	End
ENSE00001508613	30425380	30425926

Expression profiles

Bgee: expression breadth tissue_specific, 3 present calls, max score 51.19.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	51.19	silver quality
colonic epithelium	UBERON:0000397	37.20	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
sural nerve	UBERON:0015488	35.80	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
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
liver	UBERON:0002107	28.67	gold quality
monocyte	CL:0000576	28.28	silver quality
leukocyte	CL:0000738	28.22	silver quality
duodenum	UBERON:0002114	28.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.82	silver quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
cortex of kidney	UBERON:0001225	26.37	silver quality
gall bladder	UBERON:0002110	25.98	gold quality
placenta	UBERON:0001987	25.81	gold quality
blood	UBERON:0000178	25.79	gold quality
calcaneal tendon	UBERON:0003701	25.22	gold quality
muscle of leg	UBERON:0001383	24.89	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
kidney	UBERON:0002113	24.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.65

Regulation

Is transcription factor: no

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap13-23	ENSMUSG00000009047
mus_musculus	Krtap13-21	ENSMUSG00000048830
mus_musculus	Krtap13	ENSMUSG00000050224
mus_musculus	Krtap13-20	ENSMUSG00000068078
mus_musculus	Krtap13-24	ENSMUSG00000116636
rattus_norvegicus	Krtap14l	ENSRNOG00000042680
rattus_norvegicus	Krtap13-2	ENSRNOG00000063259
rattus_norvegicus	Krtap13	ENSRNOG00000063483
rattus_norvegicus	LOC100363236	ENSRNOG00000065419
rattus_norvegicus		ENSRNOG00000070302
rattus_norvegicus		ENSRNOG00000080953

Paralogs (8): KRTAP11-1 (ENSG00000182591), KRTAP13-2 (ENSG00000182816), KRTAP15-1 (ENSG00000186970), KRTAP13-4 (ENSG00000186971), KRTAP26-1 (ENSG00000197683), KRTAP13-1 (ENSG00000198390), KRTAP27-1 (ENSG00000206107), KRTAP25-1 (ENSG00000232263)

Protein

Protein identifiers

Keratin-associated protein 13-3 — Q3SY46 (reviewed: Q3SY46)

All UniProt accessions (1): Q3SY46

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.

Similarity. Belongs to the PMG family.

RefSeq proteins (1): NP_853653* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007951	KRTAP_PMG	Family

Pfam: PF05287

UniProt features (10 total): repeat 5, sequence conflict 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3SY46-F1	44.80	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_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, SUPT16H_TARGET_GENES, CRX_Q4, GSE21670_UNTREATED_VS_IL6_TREATED_CD4_TCELL_UP, TATAAA_TATA_01, GSE22342_CD11C_HIGH_VS_LOW_DECIDUAL_MACROPHAGES_DN

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

178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP13-3	KRTAP24-1	Q3LI83	860
KRTAP13-3	KRTAP22-1	Q3MIV0	795
KRTAP13-3	KRTAP20-1	Q3LI63	795
KRTAP13-3	KRTAP20-2	Q3LI61	792
KRTAP13-3	KRTAP7-1	Q8IUC3	773
KRTAP13-3	PRAMEF2	O60811	772
KRTAP13-3	KRTAP6-2	Q3LI66	772
KRTAP13-3	SCYGR1	A0A286YEY9	771
KRTAP13-3	KRTAP8-1	Q8IUC2	753
KRTAP13-3	KRTAP6-3	Q3LI67	720
KRTAP13-3	KRTAP11-1	Q8IUC1	698
KRTAP13-3	KRTAP26-1	Q6PEX3	697
KRTAP13-3	KRTAP6-1	Q3LI64	690
KRTAP13-3	KRTAP27-1	Q3LI81	667
KRTAP13-3	KRTAP1-4	P0C5Y4	640

IntAct

245 interactions, top by confidence:

A	B	Type	Score
KRTAP13-3	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
FAH	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
DTX2	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
CCDC57	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
TCP11	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
TRIM59	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP13-3	KPRP	psi-mi:“MI:0915”(physical association)	0.560
	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP13-3	NEK6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP13-3	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP13-3	LNX1	psi-mi:“MI:0915”(physical association)	0.560
CLIC3	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP13-3	TOLLIP	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
OTX1	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
VWC2	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP13-3	KRTAP3-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP13-3	CCDC120	psi-mi:“MI:0915”(physical association)	0.560
KRTAP13-3	PCSK5	psi-mi:“MI:0915”(physical association)	0.560
FOXH1	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
EFEMP2	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (85): NOTCH2NL (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid), KRTAP13-3 (Two-hybrid)

ESM2 similar proteins: A8MUX0, O08640, O13152, O93499, O93500, P02438, P02439, P02440, P02448, P02449, P02450, P02451, P04458, P04459, P07521, P08131, P08335, P20307, P20308, P25692, P60329, Q05B44, Q24JX9, Q28580, Q3LI76, Q3LI77, Q3LI83, Q3SY46, Q4W7G7, Q4W7G8, Q4W7G9, Q4W7H0, Q4W7H1, Q52LG2, Q6PEX3, Q6R645, Q6R648, Q8IUC0, Q8IUC1, Q8IUC3

Diamond homologs: A1A580, Q3LI77, Q3SY46, Q4W7H0, Q4W7H1, Q52LG2, Q8IUC0, O08640, Q3LI76, Q4W7G7, Q4W7G8, Q4W7G9, Q6R645, Q9QZU5, Q8IUC1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 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	9	13.6×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	22
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
236547	GRCh38/hg38 21q21.1-22.11(chr21:21754822-32380347)	Pathogenic
686229	GRCh37/hg19 21q11.2-22.3(chr21:15006457-48097372)x3	Pathogenic

SpliceAI

219 predictions. Top by Δscore:

Variant	Effect	Δscore
21:30425861:AACCC:A	donor_gain	0.8500
21:30425861:AACC:A	donor_gain	0.8400
21:30425865:C:CA	donor_gain	0.8400
21:30425701:A:C	donor_gain	0.7600
21:30425716:CAG:C	donor_gain	0.7600
21:30425660:T:TA	donor_gain	0.7500
21:30425700:A:AC	donor_gain	0.7500
21:30425529:T:C	donor_gain	0.6900
21:30425714:G:T	donor_gain	0.6900
21:30425859:G:C	donor_gain	0.6900
21:30425698:TCAA:T	donor_gain	0.6800
21:30425699:CAAC:C	donor_gain	0.6800
21:30425700:AACA:A	donor_gain	0.6800
21:30425897:A:AT	donor_gain	0.6600
21:30425763:G:C	donor_gain	0.6500
21:30425861:AAC:A	donor_gain	0.6400
21:30425806:TAG:T	donor_gain	0.6300
21:30425807:AGA:A	donor_gain	0.6300
21:30425623:A:C	donor_gain	0.6100
21:30425699:CA:C	donor_gain	0.6000
21:30425700:AA:A	donor_gain	0.6000
21:30425718:G:C	donor_gain	0.6000
21:30425658:AGT:A	donor_gain	0.5900
21:30425808:G:GT	donor_gain	0.5900
21:30425866:C:A	donor_gain	0.5900
21:30425442:C:CT	donor_gain	0.5800
21:30425705:A:AC	donor_gain	0.5800
21:30425706:C:CC	donor_gain	0.5800
21:30425765:A:AT	donor_gain	0.5800
21:30425861:A:T	donor_gain	0.5800

AlphaMissense

1124 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:30425400:G:C	F171L	0.844
21:30425400:G:T	F171L	0.844
21:30425402:A:G	F171L	0.844
21:30425532:G:C	F127L	0.788
21:30425532:G:T	F127L	0.788
21:30425534:A:G	F127L	0.788
21:30425883:G:C	F10L	0.772
21:30425883:G:T	F10L	0.772
21:30425885:A:G	F10L	0.772
21:30425439:G:C	F158L	0.764
21:30425439:G:T	F158L	0.764
21:30425441:A:G	F158L	0.764
21:30425475:G:C	F146L	0.747
21:30425475:G:T	F146L	0.747
21:30425477:A:G	F146L	0.747
21:30425457:A:C	F152L	0.734
21:30425457:A:T	F152L	0.734
21:30425459:A:G	F152L	0.734
21:30425607:A:C	F102L	0.699
21:30425607:A:T	F102L	0.699
21:30425609:A:G	F102L	0.699
21:30425415:G:C	F166L	0.585
21:30425415:G:T	F166L	0.585
21:30425417:A:G	F166L	0.585

dbSNP variants (sampled 300 via entrez): RS1000953923 (21:30427184 A>T), RS1001059639 (21:30427784 G>A), RS1001646093 (21:30425123 T>C), RS1004179888 (21:30424921 A>C), RS1004779197 (21:30426335 C>T), RS1004846925 (21:30427876 T>C,G), RS1005213875 (21:30426773 C>T), RS1005596669 (21:30427334 A>G), RS1008319089 (21:30427798 T>C), RS1008425669 (21:30425278 G>C), RS1008626267 (21:30426109 T>C), RS1008704032 (21:30427527 A>T), RS1009073770 (21:30426235 A>G), RS1009753073 (21:30427055 T>C), RS1010739772 (21:30426403 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): monosomy 21 (MONDO:0018930)

Orphanet (1): 21q deletion syndrome (Orphanet:574)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537108	Chromosome 21 monosomy (supp.)

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
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Malathion	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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