KRABD3

Summary

KRABD3 (KRAB domain containing 3, HGNC:22228) is a protein-coding gene on chromosome 7q36.1, encoding KRAB domain-containing protein 3 (A5PL33).

Predicted to be involved in regulation of DNA-templated transcription.

Source: NCBI Gene 84626 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 131 total
• MANE Select transcript: NM_001290187

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22228
Approved symbol	KRABD3
Name	KRAB domain containing 3
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1862
Ensembl gene	ENSG00000133619
Ensembl biotype	protein_coding
Entrez	84626

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000319551, ENST00000467333, ENST00000485033, ENST00000486744, ENST00000489951, ENST00000496080, ENST00000496259, ENST00000497895, ENST00000621069, ENST00000881409, ENST00000881410, ENST00000881411, ENST00000881412, ENST00000915867, ENST00000915868, ENST00000915869, ENST00000945700, ENST00000945701, ENST00000945702, ENST00000945703, ENST00000945704, ENST00000945705, ENST00000945706, ENST00000945707

RefSeq mRNA: 17 — MANE Select: NM_001290187 NM_001290187, NM_001394478, NM_001394479, NM_001394480, NM_001394481, NM_001394482, NM_001394483, NM_001394484, NM_001394485, NM_001394486, NM_001394487, NM_001394488, NM_001394489, NM_001394490, NM_001394491, NM_001394492, NM_032534

CCDS: CCDS75674, CCDS78285, CCDS94228

Canonical transcript exons

ENST00000496259 — 17 exons

Exon	Start	End
ENSE00003490678	149720008	149720127
ENSE00003518351	149730428	149730568
ENSE00003534775	149728523	149728675
ENSE00003537779	149724652	149724849
ENSE00003541872	149722422	149722553
ENSE00003583141	149730147	149730341
ENSE00003622794	149721383	149721535
ENSE00003630739	149722783	149722956
ENSE00003677341	149725315	149725488
ENSE00003680018	149733206	149734575
ENSE00003686828	149731672	149731776
ENSE00003687038	149725887	149726060
ENSE00003693732	149723734	149723889
ENSE00003740269	149729188	149729370
ENSE00003751718	149714951	149715066
ENSE00003755763	149719546	149719672
ENSE00003787844	149720835	149720990

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 95.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0002 / max 65.7214, expressed in 1572 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81897	3.2083	1371
81896	0.8039	426
81899	0.5460	292
81898	0.2849	121
81901	0.1571	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	95.76	silver quality
apex of heart	UBERON:0002098	93.15	gold quality
right atrium auricular region	UBERON:0006631	91.89	gold quality
cardiac atrium	UBERON:0002081	91.48	gold quality
adenohypophysis	UBERON:0002196	90.78	gold quality
pituitary gland	UBERON:0000007	89.42	gold quality
heart left ventricle	UBERON:0002084	89.28	gold quality
cardiac ventricle	UBERON:0002082	88.76	gold quality
heart	UBERON:0000948	87.60	gold quality
myocardium	UBERON:0002349	87.51	silver quality
kidney epithelium	UBERON:0004819	87.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.67	gold quality
cerebellar hemisphere	UBERON:0002245	84.79	gold quality
right frontal lobe	UBERON:0002810	84.69	gold quality
cerebellar cortex	UBERON:0002129	84.55	gold quality
germinal epithelium of ovary	UBERON:0001304	84.03	silver quality
mucosa of stomach	UBERON:0001199	83.60	gold quality
cerebellum	UBERON:0002037	83.56	gold quality
body of uterus	UBERON:0009853	82.95	gold quality
ectocervix	UBERON:0012249	82.66	gold quality
right ovary	UBERON:0002118	82.33	gold quality
anterior cingulate cortex	UBERON:0009835	82.22	gold quality
metanephros cortex	UBERON:0010533	82.03	gold quality
ascending aorta	UBERON:0001496	81.66	gold quality
thoracic aorta	UBERON:0001515	81.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.60	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.60	gold quality
tibial nerve	UBERON:0001323	81.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.54	gold quality
lower esophagus	UBERON:0013473	81.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting KRABD3, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-1302	97.92	67.27	844
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4298	97.26	66.59	765
HSA-MIR-1224-3P	97.24	65.92	851
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-4772-5P	95.60	68.04	617
HSA-MIR-4524B-3P	95.52	64.12	964

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krba1	ENSMUSG00000042810
rattus_norvegicus	Krba1	ENSRNOG00000007405

Protein

Protein identifiers

KRAB domain-containing protein 3 — A5PL33 (reviewed: A5PL33)

All UniProt accessions (6): A0A087WVC5, A0A0C4DH65, A5PL33, C9J5U6, C9JYG0, H7C530

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in brain (cerebellum).

Isoforms (3)

UniProt ID	Names	Canonical?
A5PL33-1	1	yes
A5PL33-2	2
A5PL33-3	3

RefSeq proteins (17): NP_001277116, NP_001381407, NP_001381408, NP_001381409, NP_001381410, NP_001381411, NP_001381412, NP_001381413, NP_001381414, NP_001381415, NP_001381416, NP_001381417, NP_001381418, NP_001381419, NP_001381420, NP_001381421, NP_115923 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029317	KRBA1_rpt	Repeat
IPR040095	KRBA1	Family

Pfam: PF15287

UniProt features (35 total): compositionally biased region 16, modified residue 7, region of interest 6, splice variant 2, sequence variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5PL33-F1	42.56	0.02

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 101, 177, 182, 184, 229, 253, 355

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: 100 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, WONG_ADULT_TISSUE_STEM_MODULE, KOYAMA_SEMA3B_TARGETS_DN, WIERENGA_STAT5A_TARGETS_UP, WIERENGA_STAT5A_TARGETS_GROUP1, KRIEG_HYPOXIA_NOT_VIA_KDM3A, FOSTER_KDM1A_TARGETS_DN, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, KUMAR_AUTOPHAGY_NETWORK, AKT_UP_MTOR_DN.V1_DN, MTOR_UP.V1_UP, GSE14415_FOXP3_KO_NATURAL_TREG_VS_TCONV_UP, GSE14415_INDUCED_TREG_VS_FOXP3_KO_INDUCED_TREG_UP, CBX5_TARGET_GENES

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), biological_process (GO:0008150)

GO Molecular Function (1): molecular_function (GO:0003674)

GO Cellular Component (1): cellular_component (GO:0005575)

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

Protein interactions and networks

STRING

570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRABD3	LRRC61	Q9BV99	613
KRABD3	ZBED10P	Q96FA7	574
KRABD3	ZNF696	Q9H7X3	535
KRABD3	CCDC13	Q8IYE1	530
KRABD3	C7orf33	Q8WU49	478
KRABD3	FAM86B1	Q8N7N1	476
KRABD3	LYG2	Q86SG7	472
KRABD3	METTL25B	Q96FB5	463
KRABD3	CLEC2A	Q6UVW9	449
KRABD3	DRC11L	A6NCM1	448
KRABD3	ATP6V0E2	Q8NHE4	446
KRABD3	SEL1L3	Q68CR1	440
KRABD3	WDR86	Q86TI4	439
KRABD3	A0A087WTJ2	A0A087WTJ2	432
KRABD3	CCDC9B	Q6ZUT6	431

IntAct

33 interactions, top by confidence:

A	B	Type	Score
KRBA1	TRIM27	psi-mi:“MI:0914”(association)	0.530
Dlg4	KRBA1	psi-mi:“MI:0407”(direct interaction)	0.440
GSK3A	KRBA1	psi-mi:“MI:0915”(physical association)	0.400
KRBA1	GSK3B	psi-mi:“MI:0915”(physical association)	0.400
KRBA1	PLK1	psi-mi:“MI:0915”(physical association)	0.370
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
CDC16	IFT56	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
PNMA2	TARS3	psi-mi:“MI:0914”(association)	0.350
TRIM52	MEIOC	psi-mi:“MI:0914”(association)	0.350
DPP8	KRBA1	psi-mi:“MI:0914”(association)	0.350
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
KLHL20	KRBA1	psi-mi:“MI:0914”(association)	0.350
TFPT	KRBA1	psi-mi:“MI:0914”(association)	0.350
RFPL4B	KRBA1	psi-mi:“MI:0914”(association)	0.350
C6orf141	KRBA1	psi-mi:“MI:0914”(association)	0.350
EFNB1	KRBA1	psi-mi:“MI:0914”(association)	0.350
PRMT2	KRBA1	psi-mi:“MI:0914”(association)	0.350
THSD4	KRBA1	psi-mi:“MI:0914”(association)	0.350
KRT38	KRBA1	psi-mi:“MI:0914”(association)	0.350
P4HA2	KRBA1	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
CELA1	KRBA1	psi-mi:“MI:0914”(association)	0.350
P3H1	KRBA1	psi-mi:“MI:0914”(association)	0.350
ZNF738	KRBA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (61): KRBA1 (Affinity Capture-MS), KRBA1 (Affinity Capture-MS), KRBA1 (Affinity Capture-MS), SHCBP1 (Affinity Capture-MS), P3H2 (Affinity Capture-MS), TBCCD1 (Affinity Capture-MS), KRBA1 (Affinity Capture-MS), PPP2R3B (Affinity Capture-MS), KRBA1 (Affinity Capture-MS), KRBA1 (Affinity Capture-MS), KRBA1 (Affinity Capture-MS), KRBA1 (Affinity Capture-MS), ZMYND19 (Affinity Capture-MS), KRBA1 (Affinity Capture-MS), KRBA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

Diamond homologs: A5PL33, Q6NXZ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2977 predictions. Top by Δscore:

Variant	Effect	Δscore
7:149719669:GTGG:G	donor_gain	1.0000
7:149719671:GG:G	donor_gain	1.0000
7:149719672:GG:G	donor_gain	1.0000
7:149719673:G:GA	donor_loss	1.0000
7:149720832:CAGG:C	acceptor_loss	1.0000
7:149720833:A:AG	acceptor_gain	1.0000
7:149720833:AGG:A	acceptor_gain	1.0000
7:149720833:AGGG:A	acceptor_gain	1.0000
7:149720834:G:GG	acceptor_gain	1.0000
7:149720834:GGG:G	acceptor_gain	1.0000
7:149720834:GGGG:G	acceptor_gain	1.0000
7:149720987:GAGG:G	donor_gain	1.0000
7:149720988:AGGG:A	donor_loss	1.0000
7:149720989:GG:G	donor_gain	1.0000
7:149720989:GGGTA:G	donor_loss	1.0000
7:149720990:GG:G	donor_gain	1.0000
7:149720990:GGT:G	donor_loss	1.0000
7:149720991:G:GG	donor_gain	1.0000
7:149720992:T:G	donor_loss	1.0000
7:149721518:G:T	donor_gain	1.0000
7:149723732:A:AG	acceptor_gain	1.0000
7:149723733:G:GG	acceptor_gain	1.0000
7:149725885:A:AG	acceptor_gain	1.0000
7:149725886:G:GG	acceptor_gain	1.0000
7:149728518:CACA:C	acceptor_loss	1.0000
7:149728521:A:AC	acceptor_loss	1.0000
7:149728522:G:GC	acceptor_loss	1.0000
7:149728671:GGAAG:G	donor_gain	1.0000
7:149728672:G:GT	donor_gain	1.0000
7:149728673:A:T	donor_gain	1.0000

AlphaMissense

6779 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:149720900:T:C	F74L	0.989
7:149720902:C:A	F74L	0.989
7:149720902:C:G	F74L	0.989
7:149725360:T:C	L391P	0.986
7:149720880:T:C	L67P	0.985
7:149720037:T:C	F22L	0.983
7:149720039:C:A	F22L	0.983
7:149720039:C:G	F22L	0.983
7:149722828:T:C	L215P	0.980
7:149725348:T:C	L387P	0.979
7:149733395:T:C	L814P	0.978
7:149720892:T:C	I71T	0.975
7:149722816:T:C	L211P	0.975
7:149733383:T:C	L810P	0.972
7:149720871:T:C	L64P	0.968
7:149719650:C:A	N4K	0.965
7:149719650:C:G	N4K	0.965
7:149730224:T:C	F630L	0.965
7:149730226:C:A	F630L	0.965
7:149730226:C:G	F630L	0.965
7:149720038:T:C	F22S	0.964
7:149722816:T:A	L211H	0.964
7:149730180:T:C	L615P	0.962
7:149720892:T:G	I71S	0.960
7:149725348:T:A	L387Q	0.960
7:149720904:T:C	L75S	0.959
7:149733362:T:C	L803P	0.958
7:149733404:T:C	L817P	0.958
7:149720901:T:C	F74S	0.956
7:149720871:T:A	L64Q	0.954

dbSNP variants (sampled 300 via entrez): RS1000044972 (7:149722923 G>C), RS1000195679 (7:149715788 G>A), RS1000542714 (7:149715509 G>T), RS1000683299 (7:149732075 T>C), RS1000697953 (7:149731725 A>C,G), RS1001062096 (7:149731815 A>G,T), RS1001117193 (7:149732091 C>T), RS1001394320 (7:149717321 G>A,T), RS1001602011 (7:149714690 G>A), RS1001784694 (7:149729689 G>A), RS1001993044 (7:149726651 T>C), RS1002020235 (7:149714328 A>G), RS1002069946 (7:149715721 G>T), RS1002188807 (7:149725153 G>A,C), RS1002279332 (7:149725668 C>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005547_8	Major depressive disorder	5.000000e-07
GCST007829_2	Systolic blood pressure	2.000000e-08
GCST008765_4	Perceived intensity of aspartame	1.000000e-06
GCST008766_3	Perceived intensity of sweet substances	7.000000e-06
GCST009066_13	Mosaic loss of chromosome Y (Y chromosome dosage)	1.000000e-19
GCST009067_15	Mosaic loss of chromosome Y (Y chromosome dosage)	1.000000e-34
GCST90002400_62	Plateletcrit	6.000000e-15
GCST90002402_40	Platelet count	3.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006944	systolic blood pressure change measurement
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
sodium arsenite	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
nutlin 3	increases expression, affects cotreatment	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	increases abundance, affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery