KRABD5

Summary

KRABD5 (KRAB domain containing 5, HGNC:26987) is a protein-coding gene on chromosome 16p11.2, encoding KRAB domain-containing protein 5 (Q7Z2F6). It is a selective cancer dependency (DepMap: 25.7% of cell lines).

Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to be located in nucleus.

Source: NCBI Gene 124411 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 18 total
• Cancer dependency (DepMap): dependent in 25.7% of screened cell lines
• MANE Select transcript: NM_001130913

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26987
Approved symbol	KRABD5
Name	KRAB domain containing 5
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000197302
Ensembl biotype	protein_coding
Entrez	124411

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 12 protein_coding, 5 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000316491, ENST00000398696, ENST00000398707, ENST00000529515, ENST00000529943, ENST00000530881, ENST00000531864, ENST00000533488, ENST00000534277, ENST00000534369, ENST00000539915, ENST00000542684, ENST00000544044, ENST00000689850, ENST00000692451, ENST00000693662, ENST00000932490, ENST00000932491, ENST00000932492, ENST00000932493, ENST00000969943

RefSeq mRNA: 15 — MANE Select: NM_001130913 NM_001130913, NM_001394173, NM_001394174, NM_001394175, NM_001394176, NM_001394177, NM_001394178, NM_001394179, NM_001394180, NM_001394181, NM_001394182, NM_001394183, NM_001394184, NM_001394185, NM_001394186

CCDS: CCDS45473, CCDS92144, CCDS92145

Canonical transcript exons

ENST00000316491 — 5 exons

Exon	Start	End
ENSE00001316085	31713244	31713435
ENSE00001400113	31759357	31761565
ENSE00003507484	31722626	31722752
ENSE00003617132	31753766	31753900
ENSE00003636005	31723258	31723353

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 92.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.6780 / max 314.0592, expressed in 1794 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153849	13.9999	1792
153850	1.6780	804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	92.69	gold quality
esophagus squamous epithelium	UBERON:0006920	92.56	gold quality
germinal epithelium of ovary	UBERON:0001304	91.31	gold quality
pylorus	UBERON:0001166	90.48	gold quality
pericardium	UBERON:0002407	90.45	gold quality
superior surface of tongue	UBERON:0007371	90.34	gold quality
upper arm skin	UBERON:0004263	90.00	gold quality
endothelial cell	CL:0000115	89.46	gold quality
palpebral conjunctiva	UBERON:0001812	89.42	gold quality
visceral pleura	UBERON:0002401	89.40	gold quality
pharyngeal mucosa	UBERON:0000355	89.01	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.84	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.45	gold quality
calcaneal tendon	UBERON:0003701	88.37	gold quality
colonic epithelium	UBERON:0000397	88.25	gold quality
tibia	UBERON:0000979	88.24	gold quality
oocyte	CL:0000023	88.09	gold quality
islet of Langerhans	UBERON:0000006	88.09	gold quality
thymus	UBERON:0002370	88.09	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.03	gold quality
secondary oocyte	CL:0000655	87.97	gold quality
tongue	UBERON:0001723	87.89	gold quality
substantia nigra pars compacta	UBERON:0001965	87.76	gold quality
pons	UBERON:0000988	87.75	gold quality
layer of synovial tissue	UBERON:0007616	87.67	gold quality
vena cava	UBERON:0004087	87.56	gold quality
parietal pleura	UBERON:0002400	87.53	gold quality
renal medulla	UBERON:0000362	87.42	gold quality
gingival epithelium	UBERON:0001949	87.29	gold quality
cardia of stomach	UBERON:0001162	87.21	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.28
E-MTAB-6386	no	132.84

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.7% of screened cell lines.

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkeyp-19e1.4	ENSDARG00000094163

Paralogs (1): ZNF862 (ENSG00000106479)

Protein

Protein identifiers

KRAB domain-containing protein 5 — Q7Z2F6 (reviewed: Q7Z2F6)

All UniProt accessions (9): A0A8I5KVP7, A0A8I5KY90, E9PKP5, E9PLE2, E9PMU6, E9PRX5, F5GWD4, F8WER7, Q7Z2F6

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z2F6-1	1	yes
Q7Z2F6-2	2

RefSeq proteins (15): NP_001124385, NP_001381102, NP_001381103, NP_001381104, NP_001381105, NP_001381106, NP_001381107, NP_001381108, NP_001381109, NP_001381110, NP_001381111, NP_001381112, NP_001381113, NP_001381114, NP_001381115 (=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 (5 total): splice variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z2F6-F1	70.22	0.24

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: 40 (showing top): chr16p11, LEE_RECENT_THYMIC_EMIGRANT, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES, CHAF1B_TARGET_GENES, RUVBL1_TARGET_GENES, SETD7_TARGET_GENES, ZFP28_TARGET_GENES, ZSCAN30_TARGET_GENES, MIR3671, MIR493_5P

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

GO Molecular Function (4): DNA binding (GO:0003677), protein binding (GO:0005515), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

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
nucleic acid binding	1
binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRABD5	FAM86C1P	Q9NVL1	480
KRABD5	FLYWCH2	Q96CP2	473
KRABD5	PPP1R21	Q6ZMI0	431
KRABD5	MOSMO	Q8NHV5	420
KRABD5	MFSD11	O43934	415
KRABD5	Q92681	Q92681	403
KRABD5	STON1	Q9Y6Q2	400
KRABD5	ERI2	A8K979	396
KRABD5	WDR90	Q96KV7	376
KRABD5	EFCAB6	Q5THR3	374
KRABD5	METTL23	Q86XA0	370
KRABD5	S100PBP	Q96BU1	357
KRABD5	MRPL37	Q9BZE1	355
KRABD5	OLIG3	Q7RTU3	353
KRABD5	PDGFC	Q9NRA1	353

IntAct

12 interactions, top by confidence:

A	B	Type	Score
VAC14	KRBOX5	psi-mi:“MI:0915”(physical association)	0.560
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.350
KRBOX5	VAC14	psi-mi:“MI:0915”(physical association)	0.000
secA	KRBOX5	psi-mi:“MI:0915”(physical association)	0.000
rpoB	KRBOX5	psi-mi:“MI:0915”(physical association)	0.000
fusA	KRBOX5	psi-mi:“MI:0915”(physical association)	0.000
sfcA2	KRBOX5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): ZNF720 (Affinity Capture-MS), ZNF720 (Two-hybrid), ZNF720 (Affinity Capture-MS), ZNF720 (Affinity Capture-MS), ZNF720 (Affinity Capture-MS), ZNF720 (Affinity Capture-RNA), APP (Reconstituted Complex)

ESM2 similar proteins: A0RZ79, A0T0Z7, A1AVW3, A8AZ80, A8GAT9, A9A5W9, B0TC60, B1GZ87, B1HMX6, B2LMN4, B2VHV7, B7HHG6, B7INA4, B8CNS1, B8G1X0, C4QGM3, O48397, O48398, O98453, P03715, P04028, P21000, P38457, P38475, P43395, P52141, P52201, Q06GT5, Q083H7, Q0ANQ4, Q0VSJ9, Q250M8, Q2MIE3, Q2VED6, Q33BV4, Q3C1N3, Q3J8R8, Q45062, Q4ZZG6, Q54EY1

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1308 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31722621:TTCA:T	acceptor_loss	1.0000
16:31722622:TCAG:T	acceptor_loss	1.0000
16:31722623:CAG:C	acceptor_loss	1.0000
16:31722624:A:AG	acceptor_gain	1.0000
16:31722624:A:AT	acceptor_loss	1.0000
16:31722624:AG:A	acceptor_gain	1.0000
16:31722624:AGG:A	acceptor_gain	1.0000
16:31722625:G:A	acceptor_loss	1.0000
16:31722625:G:GG	acceptor_gain	1.0000
16:31722625:GG:G	acceptor_gain	1.0000
16:31722625:GGG:G	acceptor_gain	1.0000
16:31722625:GGGA:G	acceptor_gain	1.0000
16:31722751:GG:G	donor_gain	1.0000
16:31722752:GG:G	donor_gain	1.0000
16:31722752:GGTGA:G	donor_loss	1.0000
16:31722753:G:C	donor_loss	1.0000
16:31722754:T:A	donor_loss	1.0000
16:31723147:G:GT	donor_gain	1.0000
16:31713422:G:GT	donor_gain	0.9900
16:31722625:GGGAC:G	acceptor_gain	0.9900
16:31722753:G:GG	donor_gain	0.9900
16:31723147:G:T	donor_gain	0.9900
16:31723253:AACAG:A	acceptor_loss	0.9900
16:31723255:CA:C	acceptor_loss	0.9900
16:31723349:GCCAG:G	donor_gain	0.9900
16:31723350:CCAG:C	donor_loss	0.9900
16:31723352:AGG:A	donor_loss	0.9900
16:31723354:GT:G	donor_loss	0.9900
16:31723355:T:A	donor_loss	0.9900
16:31727455:AGGC:A	donor_gain	0.9900

AlphaMissense

823 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31722638:T:C	F6L	0.953
16:31722640:C:A	F6L	0.953
16:31722640:C:G	F6L	0.953
16:31722659:T:C	F13L	0.949
16:31722661:C:A	F13L	0.949
16:31722661:C:G	F13L	0.949
16:31722660:T:C	F13S	0.917
16:31722650:G:C	A10P	0.914
16:31722697:G:C	Q25H	0.889
16:31722697:G:T	Q25H	0.889
16:31722676:G:C	W18C	0.871
16:31722676:G:T	W18C	0.871
16:31722674:T:A	W18R	0.864
16:31722674:T:C	W18R	0.864
16:31722721:G:A	M33I	0.863
16:31722721:G:C	M33I	0.863
16:31722721:G:T	M33I	0.863
16:31722639:T:C	F6S	0.835
16:31722660:T:G	F13C	0.834
16:31722730:C:A	N36K	0.833
16:31722730:C:G	N36K	0.833
16:31722705:T:C	L28S	0.832
16:31722639:T:G	F6C	0.826
16:31722726:A:T	E35V	0.821
16:31722696:A:C	Q25P	0.812
16:31723274:G:C	K49N	0.800
16:31723274:G:T	K49N	0.800
16:31722707:T:G	Y29D	0.788
16:31723290:T:C	F55L	0.783
16:31723292:T:A	F55L	0.783

dbSNP variants (sampled 300 via entrez): RS1000156792 (16:31721426 T>C), RS1000253186 (16:31723220 T>G), RS1000339605 (16:31717099 C>G,T), RS1000441882 (16:31756158 G>A), RS1000550304 (16:31750113 T>C), RS1000555064 (16:31723804 T>G), RS1000662154 (16:31748858 C>G,T), RS1000989617 (16:31721309 A>C), RS1001082017 (16:31736418 T>C), RS1001092569 (16:31744108 C>G,T), RS1001184753 (16:31757526 TA>T), RS1001377863 (16:31729742 T>G), RS1001677637 (16:31721269 T>C), RS1001781678 (16:31749676 C>T), RS1001873845 (16:31716897 T>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

0 associations (top):

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
Valproic Acid	affects expression, decreases expression, increases expression	4
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	2
dicrotophos	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	decreases expression, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Sodium Dodecyl Sulfate	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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