BCLAF3

Summary

BCLAF3 (BCLAF1 and THRAP3 family member 3, HGNC:27413) is a protein-coding gene on chromosome Xp22.12, encoding BCLAF1 and THRAP3 family member 3 (A2AJT9). Component of the spliceosome complex, important for maintaining embryonic stem cell (ESC) fate.

Predicted to enable DNA binding activity and transcription coregulator activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in mitochondrion. Predicted to be part of mediator complex.

Source: NCBI Gene 256643 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 185 total — 3 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_001367774

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27413
Approved symbol	BCLAF3
Name	BCLAF1 and THRAP3 family member 3
Location	Xp22.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000173681
Ensembl biotype	protein_coding
OMIM	301159
Entrez	256643

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 40 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000340625, ENST00000379682, ENST00000379687, ENST00000451208, ENST00000456553, ENST00000466702, ENST00000471203, ENST00000472158, ENST00000855287, ENST00000855288, ENST00000855289, ENST00000855290, ENST00000855291, ENST00000855292, ENST00000855293, ENST00000855294, ENST00000855295, ENST00000855296, ENST00000931153, ENST00000931154, ENST00000931155, ENST00000931156, ENST00000931157, ENST00000931158, ENST00000931159, ENST00000931160, ENST00000931161, ENST00000931162, ENST00000931163, ENST00000931164, ENST00000931165, ENST00000931166, ENST00000931167, ENST00000952185, ENST00000952186, ENST00000952187, ENST00000952188, ENST00000952189, ENST00000952190, ENST00000952191, ENST00000952192, ENST00000952193, ENST00000952194, ENST00000952195, ENST00000952196

RefSeq mRNA: 2 — MANE Select: NM_001367774 NM_001367774, NM_198279

CCDS: CCDS14194, CCDS94576

Canonical transcript exons

ENST00000379682 — 12 exons

Exon	Start	End
ENSE00001200039	19950753	19950868
ENSE00001200047	19952988	19953051
ENSE00001200055	19953778	19953892
ENSE00001249935	19937418	19937532
ENSE00001385885	19935809	19935898
ENSE00001482119	19912860	19917334
ENSE00001661024	19966080	19966649
ENSE00001788281	19965044	19965706
ENSE00001890884	19970224	19970298
ENSE00003468635	19955391	19955566
ENSE00003596729	19929785	19929940
ENSE00003935857	19990908	19991061

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 96.40.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.40	gold quality
oocyte	CL:0000023	93.46	gold quality
calcaneal tendon	UBERON:0003701	88.91	gold quality
cortical plate	UBERON:0005343	84.70	gold quality
sural nerve	UBERON:0015488	84.13	gold quality
colonic epithelium	UBERON:0000397	82.76	gold quality
ganglionic eminence	UBERON:0004023	82.68	gold quality
corpus epididymis	UBERON:0004359	82.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.19	gold quality
ventricular zone	UBERON:0003053	81.89	gold quality
mucosa of stomach	UBERON:0001199	81.35	gold quality
tibial nerve	UBERON:0001323	81.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.83	gold quality
popliteal artery	UBERON:0002250	80.23	gold quality
tibial artery	UBERON:0007610	80.23	gold quality
rectum	UBERON:0001052	80.11	gold quality
epithelial cell of pancreas	CL:0000083	80.05	silver quality
bone marrow cell	CL:0002092	79.69	gold quality
gastrocnemius	UBERON:0001388	79.58	gold quality
muscle of leg	UBERON:0001383	79.46	gold quality
body of uterus	UBERON:0009853	79.41	gold quality
cerebellar hemisphere	UBERON:0002245	79.35	gold quality
cerebellar cortex	UBERON:0002129	79.26	gold quality
aorta	UBERON:0000947	78.93	gold quality
transverse colon	UBERON:0001157	78.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.89	gold quality
monocyte	CL:0000576	78.74	gold quality
leukocyte	CL:0000738	78.61	gold quality
left ovary	UBERON:0002119	78.44	gold quality
ectocervix	UBERON:0012249	78.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

219 targeting BCLAF3, 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-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:112982	ENSDARG00000001829
mus_musculus	Bclaf3	ENSMUSG00000044150
rattus_norvegicus	Bclaf3	ENSRNOG00000005135

Paralogs (2): BCLAF1 (ENSG00000029363), THRAP3 (ENSG00000054118)

Protein

Protein identifiers

BCLAF1 and THRAP3 family member 3 — A2AJT9 (reviewed: A2AJT9)

Alternative names: Transient octamer binding factor 1

All UniProt accessions (3): A2AJT9, F2Z385, H7BXX2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the spliceosome complex, important for maintaining embryonic stem cell (ESC) fate. May also be involved in the negative regulation of Wnt-driven stem cell-dependent epithelial renewal in the gastric mucosa.

Subunit / interactions. Component of the spliceosome in the early G1 phase of the cell cycle in ESCs.

Subcellular location. Nucleus. Nucleus speckle.

Similarity. Belongs to the BCLAF1/THRAP3 family.

Isoforms (3)

UniProt ID	Names	Canonical?
A2AJT9-1	1	yes
A2AJT9-2	2
A2AJT9-3	3

RefSeq proteins (2): NP_001354703, NP_938020 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029199	THRAP3_BCLAF1	Family

Pfam: PF15440

UniProt features (25 total): compositionally biased region 8, modified residue 7, region of interest 4, splice variant 2, sequence conflict 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A2AJT9-F1	48.92	0.01

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 (8): 15, 17, 78, 80, 187, 402, 578, 400

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 127 (showing top): FREAC2_01, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MORF_ZNF10, FREAC3_01, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, HFH8_01, ACATTCC_MIR1_MIR206, GOBP_RNA_SPLICING, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_REGULATION_OF_STEM_CELL_POPULATION_MAINTENANCE, FREAC4_01, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, RGAGGAARY_PU1_Q6, YAMAZAKI_TCEB3_TARGETS_DN

GO Biological Process (1): positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (2): DNA binding (GO:0003677), transcription coregulator activity (GO:0003712)

GO Cellular Component (2): mitochondrion (GO:0005739), mediator complex (GO:0016592)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
nucleic acid binding	1
transcription regulator activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
core mediator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCLAF3	MAGEB3	O15480	512
BCLAF3	ZNF518A	Q6AHZ1	507
BCLAF3	PRKRA	O75569	470
BCLAF3	GAR1	Q9NY12	435
BCLAF3	MAP7D2	Q96T17	417
BCLAF3	APC2	O95996	370
BCLAF3	C11orf52	Q96A22	322
BCLAF3	PCM1	Q15154	311
BCLAF3	EXTL3	O43909	273
BCLAF3	MARK4	Q96L34	271
BCLAF3	BEX2	Q9BXY8	271
BCLAF3	ITIH1	P19827	270
BCLAF3	BEX1	Q9HBH7	269
BCLAF3	EIF2S1	P05198	260
BCLAF3	GMPS	P49915	249

IntAct

7 interactions, top by confidence:

A	B	Type	Score
Erh	BCLAF3	psi-mi:“MI:0915”(physical association)	0.400
MATR3	BCLAF3	psi-mi:“MI:0914”(association)	0.350
ERH	BCLAF3	psi-mi:“MI:0914”(association)	0.350
	RPS10-NUDT3	psi-mi:“MI:0914”(association)	0.350
EPHA1	BCLAF3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): CXorf23 (Affinity Capture-MS), CXorf23 (Affinity Capture-MS), CXorf23 (Affinity Capture-MS), CXorf23 (Affinity Capture-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS), CXorf23 (Proximity Label-MS)

ESM2 similar proteins: A0A1I8MUL8, A2AG58, A2AJT9, A6ZWC8, B3LKV0, B5VT41, B9UYK6, C1IWT1, C5IY45, C7GJ78, C8ZIQ5, E7KIY3, E7KVI3, E7M1C7, E7QAA9, E7QLB7, O14269, O23372, O94687, P0CO26, P0CO27, P11596, P30414, P30415, P33419, P97868, Q03063, Q08D57, Q18221, Q1LY77, Q23935, Q24669, Q3UC65, Q3YPH5, Q4R626, Q5LJZ2, Q5R840, Q5RAA7, Q5U2S0, Q66J90

Diamond homologs: A2AG58, A2AJT9, Q569Z6, Q5BJ39, Q5M7V8, Q9Y2W1, Q8K019, Q9NYF8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
253523	GRCh37/hg19 Xp22.33-21.3(chrX:1378591-25940311)x2	Pathogenic
58609	GRCh38/hg38 Xp22.12(chrX:19624798-20573750)x3	Pathogenic
58610	GRCh38/hg38 Xp22.12(chrX:19878110-20395102)x3	Pathogenic
3062577	GRCh37/hg19 Xp22.12(chrX:19819871-20222167)	Likely pathogenic
3062581	GRCh37/hg19 Xp22.12(chrX:19911680-20289993)	Likely pathogenic

SpliceAI

2881 predictions. Top by Δscore:

Variant	Effect	Δscore
X:19917259:C:CA	donor_gain	1.0000
X:19917267:T:TA	donor_gain	1.0000
X:19935822:A:AC	donor_gain	1.0000
X:19935823:C:CC	donor_gain	1.0000
X:19935823:CT:C	donor_gain	1.0000
X:19935894:TAATT:T	acceptor_gain	1.0000
X:19935899:C:CC	acceptor_gain	1.0000
X:19950718:C:CA	donor_gain	1.0000
X:19950789:T:C	donor_gain	1.0000
X:19953050:TCCTA:T	acceptor_loss	1.0000
X:19953053:T:C	acceptor_loss	1.0000
X:19953772:CATTA:C	donor_loss	1.0000
X:19953773:ATTAC:A	donor_loss	1.0000
X:19953774:TTA:T	donor_loss	1.0000
X:19953775:TA:T	donor_loss	1.0000
X:19953776:A:C	donor_loss	1.0000
X:19953777:C:CT	donor_loss	1.0000
X:19953888:ATTTG:A	acceptor_gain	1.0000
X:19953889:TTTG:T	acceptor_gain	1.0000
X:19953889:TTTGC:T	acceptor_loss	1.0000
X:19953890:TTG:T	acceptor_gain	1.0000
X:19953891:TG:T	acceptor_gain	1.0000
X:19953892:GC:G	acceptor_loss	1.0000
X:19953893:C:CC	acceptor_gain	1.0000
X:19953893:CTGA:C	acceptor_loss	1.0000
X:19953894:T:C	acceptor_loss	1.0000
X:19966504:T:TA	donor_gain	1.0000
X:19966515:CT:C	donor_gain	1.0000
X:19917212:AGTG:A	donor_gain	0.9900
X:19917215:G:A	donor_gain	0.9900

AlphaMissense

4740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:19950813:C:G	R562P	0.998
X:19950815:C:A	R561S	0.995
X:19950815:C:G	R561S	0.995
X:19950804:C:G	R565P	0.991
X:19950816:C:G	R561T	0.990
X:19953849:G:C	F498L	0.990
X:19953849:G:T	F498L	0.990
X:19953851:A:G	F498L	0.990
X:19955428:A:C	F471L	0.990
X:19955428:A:T	F471L	0.990
X:19955430:A:G	F471L	0.990
X:19953853:C:G	R497P	0.989
X:19950834:C:G	R555P	0.988
X:19950837:A:G	L554P	0.986
X:19953850:A:G	F498S	0.984
X:19950817:T:C	R561G	0.980
X:19950818:T:A	R560S	0.980
X:19950818:T:G	R560S	0.980
X:19950837:A:T	L554Q	0.980
X:19929862:A:C	Y677D	0.978
X:19929881:G:C	S670R	0.978
X:19929881:G:T	S670R	0.978
X:19929883:T:G	S670R	0.978
X:19950825:A:C	I558S	0.978
X:19955417:A:C	I475S	0.978
X:19955479:A:C	F454L	0.978
X:19955479:A:T	F454L	0.978
X:19955481:A:G	F454L	0.978
X:19950840:T:C	D553G	0.976
X:19955429:A:C	F471C	0.976

dbSNP variants (sampled 300 via entrez): RS1000044649 (X:19966133 C>T), RS1000118738 (X:19970956 A>C,G), RS1000177973 (X:19986665 G>A), RS1000234218 (X:19983582 G>A), RS1000240583 (X:19959121 T>A), RS1000377275 (X:19945528 C>G), RS1000398303 (X:19991859 T>G), RS1000470777 (X:19935691 T>C), RS1000473159 (X:19917695 G>A,T), RS1000555448 (X:19973070 G>T), RS1000578034 (X:19962317 G>A), RS1000614109 (X:19991392 C>A), RS1000710467 (X:19935245 G>T), RS1000753189 (X:19946757 G>C), RS1000812264 (X:19935471 C>G)

Disease associations

OMIM: gene MIM:301159 | disease phenotypes: MIM:300310

GenCC curated gene-disease

Mondo (1): immunodeficiency 61 (MONDO:0010296)

Orphanet (3): Non-syndromic agammaglobulinemia (Orphanet:229717), X-linked agammaglobulinemia (Orphanet:47), X-linked common variable immunodeficiency phenotype due to SH3KBP1 deficiency (Orphanet:696945)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002383_118	Hematocrit	1.000000e-09
GCST90002384_513	Hemoglobin	4.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538057	Agammaglobulinemia, X-linked, type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Coumestrol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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