KRABD4

Summary

KRABD4 (KRAB domain containing 4, HGNC:26007) is a protein-coding gene on chromosome Xp11.3, encoding KRAB domain-containing protein 4 (Q5JUW0).

This encodes a zinc finger protein with an N-terminal KRAB (Kruppel-associated) domain found in transcriptional repressors. This gene is located in a region of the X chromosome thought to be involved in nonsyndromic X-linked cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 55634 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001129898

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26007
Approved symbol	KRABD4
Name	KRAB domain containing 4
Location	Xp11.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20344
Ensembl gene	ENSG00000147121
Ensembl biotype	protein_coding
OMIM	300585
Entrez	55634

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 26 protein_coding, 1 retained_intron

ENST00000298190, ENST00000344302, ENST00000377919, ENST00000464900, ENST00000476762, ENST00000478600, ENST00000487081, ENST00000901194, ENST00000901195, ENST00000901196, ENST00000901197, ENST00000901198, ENST00000901199, ENST00000901200, ENST00000901201, ENST00000901202, ENST00000901203, ENST00000901204, ENST00000901205, ENST00000932354, ENST00000932355, ENST00000932356, ENST00000932357, ENST00000942304, ENST00000942305, ENST00000942306, ENST00000942307

RefSeq mRNA: 4 — MANE Select: NM_001129898 NM_001129898, NM_001129899, NM_001129900, NM_017776

CCDS: CCDS14267, CCDS48097, CCDS48098

Canonical transcript exons

ENST00000344302 — 6 exons

Exon	Start	End
ENSE00001093022	46450431	46450475
ENSE00001635850	46462748	46462874
ENSE00001743364	46463198	46463308
ENSE00001772329	46448200	46448310
ENSE00001819311	46472750	46474639
ENSE00001886612	46447297	46447346

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 86.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3630 / max 177.2784, expressed in 1772 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196119	11.6251	1763
196120	1.0124	699
196118	0.7255	430

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of uterus	UBERON:0009853	86.57	gold quality
cerebellar hemisphere	UBERON:0002245	86.55	gold quality
cerebellar cortex	UBERON:0002129	86.51	gold quality
cortical plate	UBERON:0005343	86.49	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.34	gold quality
left ovary	UBERON:0002119	86.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.08	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.01	gold quality
adrenal tissue	UBERON:0018303	85.94	gold quality
right lobe of liver	UBERON:0001114	85.93	gold quality
endocervix	UBERON:0000458	85.88	gold quality
nucleus accumbens	UBERON:0001882	85.83	gold quality
right lobe of thyroid gland	UBERON:0001119	85.68	gold quality
left lobe of thyroid gland	UBERON:0001120	85.67	gold quality
right ovary	UBERON:0002118	85.58	gold quality
cerebellum	UBERON:0002037	85.55	gold quality
visceral pleura	UBERON:0002401	85.49	gold quality
spleen	UBERON:0002106	85.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.44	gold quality
thyroid gland	UBERON:0002046	85.42	gold quality
calcaneal tendon	UBERON:0003701	85.35	gold quality
ovary	UBERON:0000992	85.09	gold quality
right coronary artery	UBERON:0001625	85.09	gold quality
colonic epithelium	UBERON:0000397	85.08	gold quality
right uterine tube	UBERON:0001302	84.89	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.89	gold quality
lower esophagus	UBERON:0013473	84.88	gold quality
parietal pleura	UBERON:0002400	84.86	gold quality
anterior cingulate cortex	UBERON:0009835	84.86	gold quality
omental fat pad	UBERON:0010414	84.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting KRABD4, 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-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-3140-3P	99.88	68.47	2069

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp78	ENSMUSG00000055150
rattus_norvegicus		ENSRNOG00000083797
drosophila_melanogaster	CG2712	FBGN0024975
drosophila_melanogaster	Phs	FBGN0036522
drosophila_melanogaster	CG3281	FBGN0260741

Paralogs (62): ZNF582 (ENSG00000018869), ZNF264 (ENSG00000083844), ZNF343 (ENSG00000088876), ZNF684 (ENSG00000117010), ZNF133 (ENSG00000125846), ZNF557 (ENSG00000130544), ZNF337 (ENSG00000130684), ZNF20 (ENSG00000132010), ZFP37 (ENSG00000136866), ZNF614 (ENSG00000142556), ZNF599 (ENSG00000153896), ZNF19 (ENSG00000157429), ZNF589 (ENSG00000164048), PRDM9 (ENSG00000164256), ZNF180 (ENSG00000167384), ZNF558 (ENSG00000167785), ZNF35 (ENSG00000169981), ZNF778 (ENSG00000170100), ZNF439 (ENSG00000171291), ZNF440 (ENSG00000171295), ZNF556 (ENSG00000172000), ZNF554 (ENSG00000172006), ZNF596 (ENSG00000172748), ZNF80 (ENSG00000174255), ZNF266 (ENSG00000174652), ZNF25 (ENSG00000175395), ZNF77 (ENSG00000175691), ZNF169 (ENSG00000175787), ZNF404 (ENSG00000176222), ZNF491 (ENSG00000177599), ZNF620 (ENSG00000177842), ZNF619 (ENSG00000177873), ZNF875 (ENSG00000181666), ZNF329 (ENSG00000181894), ZFP90 (ENSG00000184939), ZNF566 (ENSG00000186017), ZNF529 (ENSG00000186020), ZNF749 (ENSG00000186230), ZNF555 (ENSG00000186300), ZNF70 (ENSG00000187792)

Protein

Protein identifiers

KRAB domain-containing protein 4 — Q5JUW0 (reviewed: Q5JUW0)

Alternative names: KRAB box domain-containing protein 4

All UniProt accessions (3): Q5JUW0, C9J804, C9J950

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in brain, ovary, testis, prostate, tonsil, heart, bone marrow, colon, breast and kidney.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5JUW0-1	1	yes
Q5JUW0-2	2
Q5JUW0-3	3

RefSeq proteins (4): NP_001123370, NP_001123371, NP_001123372, NP_060246 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR050169	Krueppel_C2H2_ZnF	Family

Pfam: PF01352

UniProt features (6 total): splice variant 3, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JUW0-F1	49.11	0.00

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 69 (showing top): WANG_CISPLATIN_RESPONSE_AND_XPC_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, chrXp11, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, ZWANG_DOWN_BY_2ND_EGF_PULSE, MTOR_UP.N4.V1_DN, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ZIM3_TARGET_GENES, MIR616_5P, MIR371B_5P, MIR373_5P

GO Biological Process (1): regulation of DNA-templated transcription (GO:0006355)

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

GO Cellular Component (0):

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
binding	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRABD4	CHST7	Q9NS84	950
KRABD4	SLC9A7	Q96T83	881
KRABD4	ZNF391	Q9UJN7	638
KRABD4	ZNF449	Q6P9G9	623
KRABD4	TCEANC	Q8N8B7	447
KRABD4	PPP1R2C	O14990	437
KRABD4	ZNF18	P17022	429
KRABD4	ZNF492	Q9P255	418
KRABD4	DUSP21	Q9H596	405
KRABD4	DIPK2B	Q9H7Y0	397
KRABD4	ZNF711	Q9Y462	393
KRABD4	EFHC2	Q5JST6	372
KRABD4	GEMIN8	Q9NWZ8	352
KRABD4	ARMCX2	Q7L311	348
KRABD4	ZKSCAN4	Q969J2	348

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
KRBOX4	ASXL2	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): SLC25A1 (Affinity Capture-MS), STX3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), SLC25A11 (Affinity Capture-MS), KIAA0355 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), SLC43A3 (Affinity Capture-MS), SLC35F6 (Affinity Capture-MS), ASXL2 (Affinity Capture-MS), XPO5 (Affinity Capture-MS), C8orf33 (Affinity Capture-MS), SLC25A22 (Affinity Capture-MS), TMEM126A (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), FAM58A (Affinity Capture-MS)

ESM2 similar proteins: A0RZ79, A2BYT2, A2C4Z5, A8SEE4, A9A5W9, A9BCP3, A9CB83, B2XWR4, B4RL59, B7HHG6, B7HKD5, C4K7B4, C6Y4A2, G2TRU4, O28329, O29734, O29982, O74973, P03715, P38465, P39495, P41072, P41392, P62393, P83002, P84990, P86291, Q18LD6, Q2YAV1, Q3J6Q0, Q3MFB7, Q3V4Z3, Q46IR3, Q537H7, Q54J26, Q58525, Q5F861, Q5JUW0, Q5SD12, Q5UPH6

Diamond homologs: A0A1W2PQL4, A0JNB1, A0JPL0, A6NK53, A6QLU5, A6QPT6, A7MBI1, A8MT65, A8MUV8, A8MWA4, B2RXC5, B4DU55, B4DX44, E9PYI1, O14628, O75346, P0CH99, P0CI00, P17014, P17030, P17032, P17098, P51786, P85977, Q02386, Q06730, Q06732, Q0VAW7, Q12901, Q13360, Q14586, Q14588, Q14590, Q16587, Q2M3X9, Q2VY69, Q32M78, Q3ZCX4, Q49AA0, Q4R6J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1332 predictions. Top by Δscore:

Variant	Effect	Δscore
X:46462835:G:T	donor_gain	1.0000
X:46462914:G:GG	donor_gain	1.0000
X:46463196:AG:A	acceptor_gain	1.0000
X:46463197:GG:G	acceptor_gain	1.0000
X:46462742:TTACA:T	acceptor_loss	0.9900
X:46462743:TACA:T	acceptor_loss	0.9900
X:46462744:ACAGG:A	acceptor_loss	0.9900
X:46462747:G:A	acceptor_loss	0.9900
X:46462835:G:GT	donor_gain	0.9900
X:46463194:ACAG:A	acceptor_gain	0.9900
X:46463196:A:AG	acceptor_gain	0.9900
X:46463196:AGG:A	acceptor_gain	0.9900
X:46463197:G:GC	acceptor_gain	0.9900
X:46463197:GGG:G	acceptor_gain	0.9900
X:46463197:GGGT:G	acceptor_gain	0.9900
X:46472748:A:AG	acceptor_gain	0.9900
X:46472749:G:GG	acceptor_gain	0.9900
X:46472749:GAA:G	acceptor_gain	0.9900
X:46447347:G:GG	donor_gain	0.9800
X:46447361:G:GT	donor_gain	0.9800
X:46448020:G:GT	donor_gain	0.9800
X:46462741:ATTAC:A	acceptor_loss	0.9800
X:46462746:A:AG	acceptor_gain	0.9800
X:46462747:G:GG	acceptor_gain	0.9800
X:46462747:GGA:G	acceptor_gain	0.9800
X:46462834:G:GT	donor_gain	0.9800
X:46462871:GTGG:G	donor_gain	0.9800
X:46463195:CA:C	acceptor_loss	0.9800
X:46463197:G:A	acceptor_loss	0.9800
X:46447344:G:GT	donor_gain	0.9700

AlphaMissense

1131 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:46462781:T:C	F17L	0.975
X:46462783:C:A	F17L	0.975
X:46462783:C:G	F17L	0.975
X:46462848:A:T	E39V	0.973
X:46462782:T:C	F17S	0.969
X:46462819:G:C	Q29H	0.967
X:46462819:G:T	Q29H	0.967
X:46462796:T:A	W22R	0.964
X:46462796:T:C	W22R	0.964
X:46462827:T:C	L32P	0.961
X:46462874:G:T	G48W	0.959
X:46462798:G:C	W22C	0.956
X:46462798:G:T	W22C	0.956
X:46462822:G:C	K30N	0.955
X:46462822:G:T	K30N	0.955
X:46462760:T:C	F10L	0.952
X:46462762:C:A	F10L	0.952
X:46462762:C:G	F10L	0.952
X:46462849:G:C	E39D	0.952
X:46462849:G:T	E39D	0.952
X:46462852:C:A	N40K	0.950
X:46462852:C:G	N40K	0.950
X:46462772:T:C	F14L	0.946
X:46462774:T:A	F14L	0.946
X:46462774:T:G	F14L	0.946
X:46462843:G:A	M37I	0.944
X:46462843:G:C	M37I	0.944
X:46462843:G:T	M37I	0.944
X:46462806:T:C	L25P	0.938
X:46462863:T:C	L44P	0.938

dbSNP variants (sampled 300 via entrez): RS1000290993 (X:46469167 G>A), RS1000700967 (X:46456325 A>G), RS1000897773 (X:46471885 C>A), RS1000913500 (X:46462934 C>T), RS1001025559 (X:46449644 A>G), RS1001446773 (X:46448802 G>A), RS1001550458 (X:46451026 CATCTT>C), RS1001692869 (X:46446431 G>A), RS1001703186 (X:46458044 G>A), RS1001755561 (X:46457705 A>C,G,T), RS1001853440 (X:46448548 C>G), RS1001916128 (X:46452038 C>T), RS1001954775 (X:46474002 C>T), RS1001991518 (X:46446822 G>A), RS1002285846 (X:46447707 G>A)

Disease associations

OMIM: gene MIM:300585 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002403_714	Red blood cell count	4.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	2
dicrotophos	decreases expression	1
geraniol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Valproic Acid	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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