BCAS3

Summary

BCAS3 (BCAS3 microtubule associated cell migration factor, HGNC:14347) is a protein-coding gene on chromosome 17q23.2, encoding BCAS3 microtubule associated cell migration factor (Q9H6U6). Plays a role in angiogenesis.

Enables several functions, including acetyltransferase activator activity; beta-tubulin binding activity; and histone acetyltransferase binding activity. Involved in cellular response to estrogen stimulus; positive regulation of catalytic activity; and positive regulation of transcription by RNA polymerase II. Located in euchromatin; nucleus; and phagophore assembly site. Implicated in Hengel-Maroofian-Schols syndrome. Biomarker of breast cancer.

Source: NCBI Gene 54828 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): Hengel-Maroofian-Schols syndrome (Strong, GenCC)
• GWAS associations: 114 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 197 total — 2 pathogenic, 15 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈1% of expected missense variation)
• GTEx eGene: eQTL in 9 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 39
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.58 (moderately constrained)
• MANE Select transcript: NM_017679

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14347
Approved symbol	BCAS3
Name	BCAS3 microtubule associated cell migration factor
Location	17q23.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20128, PHAF2
Ensembl gene	ENSG00000141376
Ensembl biotype	protein_coding
OMIM	607470
Entrez	54828

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 20 protein_coding, 13 protein_coding_CDS_not_defined, 5 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000407086

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 3, TSL 3: 5, TSL 4: 4, TSL 5: 15

ENST00000407086, ENST00000390652, ENST00000408905, ENST00000585744, ENST00000585812, ENST00000585979, ENST00000586041, ENST00000586241, ENST00000586484, ENST00000586705, ENST00000587002, ENST00000587037, ENST00000587294, ENST00000587872, ENST00000588008, ENST00000588168, ENST00000588462, ENST00000588532, ENST00000588569, ENST00000588720, ENST00000588874, ENST00000589222, ENST00000589916, ENST00000590128, ENST00000590352, ENST00000591147, ENST00000591371, ENST00000592393, ENST00000592702, ENST00000592827, ENST00000592848, ENST00000593004, ENST00000626960, ENST00000996516, ENST00001105812, ENST00001105813, ENST00001105814, ENST00001116011, ENST00001117694, ENST00001130410, ENST00001143705

RefSeq mRNA: 8 — MANE Select: NM_017679 NM_001099432, NM_001320470, NM_001330413, NM_001330414, NM_001353144, NM_001353145, NM_001353146, NM_017679

CCDS: CCDS11626, CCDS45749, CCDS82176, CCDS82177, CCDS82178

Canonical transcript exons

ENST00000407086 — 24 exons

Exon	Start	End
ENSE00002766277	60677851	60677914
ENSE00003461111	60808004	60808076
ENSE00003478290	61015751	61015901
ENSE00003489219	61034666	61034790
ENSE00003525098	60683982	60684036
ENSE00003539906	61040792	61040892
ENSE00003551834	61084467	61084564
ENSE00003560507	61391977	61392831
ENSE00003564419	60889695	60889771
ENSE00003565063	60689686	60689761
ENSE00003570000	60902620	60902703
ENSE00003573829	61078333	61078529
ENSE00003578929	60868576	60868683
ENSE00003613162	60910532	60910702
ENSE00003624722	61368327	61368494
ENSE00003639021	60747198	60747279
ENSE00003643191	60709219	60709325
ENSE00003657120	61074920	61075020
ENSE00003661471	60924407	60924500
ENSE00003669605	60874662	60874738
ENSE00003681140	60989971	60990235
ENSE00003692889	61037889	61038054
ENSE00003693165	60679453	60679540
ENSE00003790310	60947219	60947352

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 94.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8392 / max 301.4259, expressed in 1785 samples.

Highest expression (Bgee): colonic epithelium, sural nerve, uterine tube, bone marrow cell, calcaneal tendon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BCAS3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.7e-23	-0.40	17:60677901:C:A
Testis	eqtl	2.8e-22	-0.81	17:60677901:C:A
Testis	sqtl	1.8e-16	+0.66	17:61254968:A:G
Muscle Skeletal	sqtl	1.4e-05	+0.27	17:61391581:G:A
Skin Sun Exposed Lower leg	eqtl	2.3e-04	-0.41	17:60752668:C:T
Artery Aorta	eqtl	1.2e-02	+0.36	17:60551742:G:A
Artery Tibial	eqtl	1.7e-02	-0.23	17:60950264:G:T
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-02	+0.11	17:61267960:A:G
Muscle Skeletal	eqtl	2.5e-02	+0.17	17:60677901:C:A
Brain Caudate basal ganglia	eqtl	3.6e-02	+0.61	17:59840260:T:C
Cells Cultured fibroblasts	eqtl	4.5e-02	+0.08	17:61294296:A:G

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
162056	16.2335	1783
162055	0.3658	195
162064	0.1311	56
162072	0.0992	39
162059	0.0097	5

Top tissues by expression

showing 100 of 265 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	94.37	gold quality
sural nerve	UBERON:0015488	93.72	gold quality
right uterine tube	UBERON:0001302	91.52	gold quality
bone marrow cell	CL:0002092	89.46	gold quality
calcaneal tendon	UBERON:0003701	89.23	gold quality
prefrontal cortex	UBERON:0000451	88.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.75	gold quality
right coronary artery	UBERON:0001625	88.69	gold quality
cortical plate	UBERON:0005343	88.38	gold quality
popliteal artery	UBERON:0002250	87.68	gold quality
tibial artery	UBERON:0007610	87.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.60	gold quality
frontal cortex	UBERON:0001870	86.75	gold quality
right frontal lobe	UBERON:0002810	86.75	gold quality
corpus callosum	UBERON:0002336	86.71	gold quality
aorta	UBERON:0000947	86.49	gold quality
muscle of leg	UBERON:0001383	86.24	gold quality
neocortex	UBERON:0001950	86.04	gold quality
gastrocnemius	UBERON:0001388	86.01	gold quality
left coronary artery	UBERON:0001626	85.82	gold quality
ganglionic eminence	UBERON:0004023	85.60	gold quality
epithelium of bronchus	UBERON:0002031	85.50	gold quality
right lung	UBERON:0002167	85.49	gold quality
coronary artery	UBERON:0001621	85.34	gold quality
ascending aorta	UBERON:0001496	85.16	gold quality
adrenal tissue	UBERON:0018303	85.14	gold quality
thoracic aorta	UBERON:0001515	85.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.03	gold quality
bronchus	UBERON:0002185	84.96	gold quality
descending thoracic aorta	UBERON:0002345	84.73	gold quality
skin of leg	UBERON:0001511	84.60	gold quality
apex of heart	UBERON:0002098	84.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.48	gold quality
right adrenal gland cortex	UBERON:0035827	84.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.44	gold quality
primary visual cortex	UBERON:0002436	84.34	gold quality
superior frontal gyrus	UBERON:0002661	84.20	gold quality
right adrenal gland	UBERON:0001233	84.19	gold quality
bronchial epithelial cell	CL:0002328	84.18	gold quality
anterior cingulate cortex	UBERON:0009835	84.18	gold quality
cingulate cortex	UBERON:0003027	84.17	gold quality
cerebral cortex	UBERON:0000956	84.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.15	gold quality
muscle organ	UBERON:0001630	84.08	gold quality
left adrenal gland	UBERON:0001234	83.97	gold quality
left adrenal gland cortex	UBERON:0035825	83.87	gold quality
stromal cell of endometrium	CL:0002255	83.84	gold quality
skin of abdomen	UBERON:0001416	83.83	gold quality
adrenal gland	UBERON:0002369	83.74	gold quality
corpus epididymis	UBERON:0004359	83.57	gold quality
left testis	UBERON:0004533	83.36	gold quality
leukocyte	CL:0000738	83.31	gold quality
tonsil	UBERON:0002372	83.20	gold quality
monocyte	CL:0000576	83.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.13	gold quality
lower esophagus	UBERON:0013473	83.10	gold quality
blood	UBERON:0000178	83.09	gold quality
adrenal cortex	UBERON:0001235	83.07	gold quality
spinal cord	UBERON:0002240	83.07	gold quality
granulocyte	CL:0000094	83.06	gold quality
telencephalon	UBERON:0001893	83.02	gold quality
mononuclear cell	CL:0000842	83.00	gold quality
postcentral gyrus	UBERON:0002581	82.99	gold quality
testis	UBERON:0000473	82.91	gold quality
middle temporal gyrus	UBERON:0002771	82.88	silver quality
upper lobe of left lung	UBERON:0008952	82.82	gold quality
ventricular zone	UBERON:0003053	82.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.76	gold quality
stomach	UBERON:0000945	82.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.45	gold quality
zone of skin	UBERON:0000014	82.44	gold quality
forebrain	UBERON:0001890	82.39	gold quality
ectocervix	UBERON:0012249	82.32	gold quality
right testis	UBERON:0004534	82.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.25	gold quality
tibial nerve	UBERON:0001323	82.20	gold quality
cerebellar cortex	UBERON:0002129	82.18	gold quality
esophagus	UBERON:0001043	82.13	gold quality
brain	UBERON:0000955	82.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.05	gold quality
cerebellar hemisphere	UBERON:0002245	82.03	gold quality
smooth muscle tissue	UBERON:0001135	81.92	gold quality
heart left ventricle	UBERON:0002084	81.91	gold quality
body of stomach	UBERON:0001161	81.81	gold quality
islet of Langerhans	UBERON:0000006	81.70	gold quality
caudate nucleus	UBERON:0001873	81.69	gold quality
adult mammalian kidney	UBERON:0000082	81.67	gold quality
Brodmann (1909) area 46	UBERON:0006483	81.64	gold quality
nucleus accumbens	UBERON:0001882	81.54	gold quality
hypothalamus	UBERON:0001898	81.52	gold quality
heart	UBERON:0000948	81.49	gold quality
putamen	UBERON:0001874	81.49	gold quality
Ammon’s horn	UBERON:0001954	81.49	gold quality
cerebellum	UBERON:0002037	81.48	gold quality
cardiac ventricle	UBERON:0002082	81.46	gold quality
parietal lobe	UBERON:0001872	81.44	silver quality
gall bladder	UBERON:0002110	81.44	gold quality
right atrium auricular region	UBERON:0006631	81.27	gold quality
occipital lobe	UBERON:0002021	81.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.08

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	44.7
Postcentral gyrus	tissue	44.5
Nucleus accumbens	tissue	41.1
Caudate putamen	tissue	40.4
Corpus callosum	tissue	40.1
Substantia nigra	tissue	39.7
Hippocampus	tissue	39.0	high
Frontal cortex	tissue	38.6
Locus coeruleus	tissue	38.2
Midbrain	tissue	37.8
Thalamus	tissue	37.2
Prefrontal cortex	tissue	37.0
Cerebral cortex	tissue	37.0	medium
Pons	tissue	36.9
Hippocampal formation	tissue	36.2
Somatosensory cortex	tissue	36.2
Motor cortex	tissue	35.8
Putamen	tissue	35.5
Superior colliculi	tissue	35.3
Spinal cord	tissue	35.3
Retrosplenial cortex	tissue	34.9
Medulla oblongata	tissue	34.6
Retrosplenial and cingulate cortex	tissue	34.5
Occipital cortex	tissue	34.4
Ventral forebrain	tissue	33.9
Periaqueductal gray	tissue	32.5
Entorhinal cortex	tissue	32.4
Temporal cortex	tissue	32.3
Basal ganglia	tissue	31.9	medium
Insular cortex	tissue	31.8
Hypothalamus	tissue	31.5
Cerebellum	tissue	30.3	medium
Septum	tissue	30.1
Amygdala	tissue	28.0
Olfactory bulb	tissue	23.3
Retina	tissue	16.0
Parathyroid gland	tissue	13.6	medium
Testis	tissue	13.2	medium
Fallopian tube	tissue	13.0	low
Skeletal muscle	tissue	12.8	not detected
Epididymis	tissue	11.6	medium
Liver	tissue	11.6	medium
Kidney	tissue	10.2	medium
Prostate	tissue	10.2	low
Thymus	tissue	9.8
Tongue	tissue	9.2
Placenta	tissue	9.2	medium
Vagina	tissue	8.9	low
Pancreas	tissue	8.8	medium
Lung	tissue	8.8	low
Urinary bladder	tissue	8.7	medium
Seminal vesicle	tissue	8.6	medium
Skin 1	tissue	8.5	medium
Salivary gland	tissue	8.5	medium
Esophagus	tissue	8.4	low
Smooth muscle	tissue	8.4	not detected
Thyroid gland	tissue	8.1	medium
Endometrium 1	tissue	8.0	medium
Adrenal gland	tissue	8.0	medium
Cervix	tissue	7.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Parieto-temporal junction (white matter) (63.3), Corpus callosum, genu (white matter) (58.2), Temporal white matter (56.6), Area striata (white matter) (55.6), Corpus callosum, splenium (white matter) (53.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EHMT2, ESR1, GATA3, MTA1, MTA3

miRNA regulators (miRDB)

Targeting BCAS3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

27 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-873-3P	96.84	66.09	786
HSA-MIR-6085	96.57	64.11	621
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-6753-5P	94.70	64.08	470
HSA-MIR-6813-5P	94.68	64.20	588

Functional genomics

gnomAD constraint: pLI 0.00883, LOEUF 0.58, missense Z 2.84 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000407086 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
17:60,679,458–61,368,344	807 / 1026.0	0.79	no
17:61,368,345–61,368,385	1 / 16.6	0.06	yes (p 1.3e-04)
17:61,368,386–61,392,122	109 / 122.8	0.89	no

Literature-anchored findings (GeneRIF, showing 12)

• role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells (PMID:16617102)
• BCAS3 overexpression in hormone receptor-positive premenopausal breast cancer seemed to be associated with impaired responses to tamoxifen (PMID:16855396)
• Physically associated with histone H3 and histone acetyltransferase complex protein P/CAF (p300/CBP-associated factor) and possesses histone acetyltransferase activity. (PMID:17505058)
• BCAS3 is mis-expressed in brain tumors and could serve as a human ES cell and tumor marker (PMID:18030336)
• Real-time PCR validated that up-regulation of sulphiredoxin 1 homolog (SRXN1), hemeoxygenase 1 (HMOX1), and breast carcinoma amplified sequence 3 (BCAS3) were consistently modulated. (PMID:21742584)
• BCAS3 single nucleotide polymorphism is associated with gout. (PMID:29879923)
• This study identifies the novel and essential role of Rudhira in cytoskeletal cross-talk and assigns function to the conserved BCAS3 domain. (PMID:30995157)
• Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site in response to selective and non-selective autophagy. (PMID:33499712)
• Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder. (PMID:34022130)
• Polymorphism in the GATM Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure. (PMID:34071541)
• BCAS3 exhibits oncogenic properties by promoting CRL4A-mediated ubiquitination of p53 in breast cancer. (PMID:34240781)
• BCAS3 accelerates glioblastoma tumorigenesis by restraining the P53/GADD45alpha signaling pathway. (PMID:35659972)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcas3	ENSDARG00000090764
mus_musculus	Bcas3	ENSMUSG00000059439
rattus_norvegicus	Bcas3	ENSRNOG00000066893
drosophila_melanogaster	rudhira	FBGN0266019
caenorhabditis_elegans		WBGENE00018953

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2385848) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 27 distinct phenotype terms.

Mouse phenotype (MP)	Records
embryonic growth retardation	2
embryonic lethality during organogenesis, complete penetrance	2
abnormal vascular development	1
abnormal heart morphology	1
abnormal head morphology	1
abnormal brain development	1
abnormal placenta morphology	1
abnormal visceral yolk sac morphology	1
pale yolk sac	1
disorganized yolk sac vascular plexus	1
small heart	1
abnormal vascular branching morphogenesis	1
abnormal capillary morphology	1
delayed somite formation	1
abnormal endocardium morphology	1
small placenta	1
abnormal chorionic plate morphology	1
abnormal dorsal aorta morphology	1
decreased angiogenesis	1
abnormal vascular endothelial cell morphology	1
abnormal blood vessel endothelium morphology	1
atrioventricular septal defect	1
abnormal coronary vessel morphology	1
embryonic lethality between somite formation and embryo turning, incomplete penetrance	1
decreased placental labyrinth size	1

+2 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Meyerozyma guilliermondii ATCC 6260	A5DHI9	60.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TBX2-AS1	ncRNA	103689912
BCAS3-AS1	ncRNA	107984992
TBX2	protein-coding	6909
LINC02875	ncRNA	388407
LINC01999	ncRNA	388406
PPM1D	protein-coding	8493
APPBP2	protein-coding	10513
TBX4	protein-coding	9496

Protein

Protein identifiers

BCAS3 microtubule associated cell migration factor — Q9H6U6 (reviewed: Q9H6U6)

Alternative names: Breast carcinoma-amplified sequence 3, GAOB1

All UniProt accessions (10): Q9H6U6, K7EIE2, K7EIR7, K7EJH7, K7EJU7, K7EKB0, K7ELH0, K7EML5, K7EQA6, K7ESE9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in angiogenesis. Participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge. Promotes filipodia formation. Functions synergistically with PELP1 as a transcriptional coactivator of estrogen receptor-responsive genes. Stimulates histone acetyltransferase activity. Binds to chromatin. Plays a regulatory role in autophagic activity. In complex with PHAF1, associates with the preautophagosomal structure during both non-selective and selective autophagy. Probably binds phosphatidylinositol 3-phosphate (PtdIns3P) which would mediate the recruitment preautophagosomal structures.

Subunit / interactions. Interacts with histone H3, ESR1, KAT2B and PELP1; the interactions occur in a estrogen-dependent manner. Interacts with beta-tubulin and VIM. Interacts (via C-terminal) with PHAF1; the interaction is requrired for the association with the phagophore.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Preautophagosomal structure.

Tissue specificity. Expressed in stomach, liver, lung, kidney, prostate, testis, thyroid gland, adrenal gland, brain, heart, skeletal muscle, colon, spleen, small intestine, placenta, blood leukocyte and mammary epithelial cells. Expressed in undifferentiated ES cells. Expressed in blood islands and nascent blood vessels derived from differentiated ES cells into embryoid bodies (BD). Expressed in endothelial cells. Not detected in brain. Expressed in brain tumors (at protein level). Expressed in brain. Highly expressed in breast cancers and in glioma cell lines.

Disease relevance. A chromosomal aberration involving BCAS3 has been found in some breast carcinoma cell lines. Translocation t(17;20)(q23;q13) with BCAS4. Hengel-Maroofian-Schols syndrome (HEMARS) [MIM:619641] An autosomal recessive disorder characterized by severe global developmental delay apparent from infancy or early childhood. Affected individuals have delayed walking or inability to walk, impaired intellectual development with poor or absent speech, lower limb spasticity, poor overall growth, and dysmorphic facial features. Some patients develop seizures. Brain imaging shows thinning of the posterior part of the corpus callosum, delayed myelination, and cerebral and cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Has been proposed to contain 7 WD repeats. This prediction could not be reproduced.

Induction. By estrogen.

Similarity. Belongs to the BCAS3 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9H6U6-1	2	yes
Q9H6U6-2	1
Q9H6U6-3	3
Q9H6U6-8	4
Q9H6U6-7	5, Maaab1
Q9H6U6-6	6, Maaab2

RefSeq proteins (8): NP_001092902, NP_001307399, NP_001317342, NP_001317343, NP_001340073, NP_001340074, NP_001340075, NP_060149* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR022175	BCAS3_dom	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045142	BCAS3-like	Family
IPR048382	BCAS3_WD40	Domain

Pfam: PF12490, PF21034

UniProt features (52 total): sequence variant 10, mutagenesis site 9, sequence conflict 8, modified residue 7, region of interest 5, compositionally biased region 4, splice variant 4, cross-link 2, chain 1, repeat 1, site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6U6-F1	65.25	0.31

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

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

Catalytic / active sites (1)

Position	Role
824–825	breakpoint for translocation to form bcas4-bcas3

Post-translational modifications (9)

Type	Positions
N-acetylmethionine	1
Phosphoserine	461, 480, 488, 838, 886, 898
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	215
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	215

Mutagenesis-validated functional residues (9)

Position	Phenotype
350	no effect on recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
370	decreases recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
372	no effect on recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
377	no effect on recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
400	decreases recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
401	almost abolishes recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
426	decreases recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
428	almost abolishes recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
430	almost abolishes recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 0 (showing top):

GO Biological Process (11): angiogenesis (GO:0001525), DNA-templated transcription (GO:0006351), autophagy (GO:0006914), cell-cell signaling (GO:0007267), positive regulation of endothelial cell migration (GO:0010595), regulation of actin cytoskeleton organization (GO:0032956), response to starvation (GO:0042594), positive regulation of catalytic activity (GO:0043085), response to estrogen (GO:0043627), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to estrogen stimulus (GO:0071391)

GO Molecular Function (8): chromatin binding (GO:0003682), acetyltransferase activator activity (GO:0010698), nuclear receptor binding (GO:0016922), histone acetyltransferase binding (GO:0035035), phosphatidylinositol binding (GO:0035091), histone binding (GO:0042393), beta-tubulin binding (GO:0048487), protein binding (GO:0005515)

GO Cellular Component (8): phagophore assembly site (GO:0000407), euchromatin (GO:0000791), nucleus (GO:0005634), cytoplasm (GO:0005737), cytoplasmic microtubule (GO:0005881), cell leading edge (GO:0031252), intermediate filament cytoskeleton (GO:0045111), cytoskeleton (GO:0005856)

GO top-level categories

42 GO namespaces:

Category	Terms
cellular anatomical structure	3
binding	2
cytoplasm	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
gene expression	1
RNA biosynthetic process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cell communication	1
signaling	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
response to stress	1
response to nutrient levels	1
catalytic activity	1
positive regulation of molecular function	1
regulation of catalytic activity	1
response to hormone	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cellular response to hormone stimulus	1
response to estrogen	1
enzyme activator activity	1
acetyltransferase activity	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
enzyme binding	1
anion binding	1
protein binding	1
tubulin binding	1
chromatin	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
microtubule	1
cytoskeleton	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 15 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

15 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to estrogen stimulus	BP	direct assay
positive regulation of catalytic activity	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
response to estrogen	BP	direct assay
cytoplasm	CC	direct assay
euchromatin	CC	direct assay
nucleus	CC	direct assay
phagophore assembly site	CC	direct assay
acetyltransferase activator activity	MF	direct assay
beta-tubulin binding	MF	direct assay
chromatin binding	MF	direct assay
histone acetyltransferase binding	MF	physical interaction
histone binding	MF	direct assay
nuclear receptor binding	MF	physical interaction
phosphatidylinositol binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,034 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCAS3	BCAS4	Q8TDM0	969
BCAS3	TBX4	P57082	685
BCAS3	MTA1	Q13330	665
BCAS3	TBX2	Q13207	618
BCAS3	PHAF1	Q9BSU1	523
BCAS3	ESR1	P03372	491
BCAS3	PLEKHG1	Q9ULL1	468
BCAS3	APPBP2	Q92624	458
BCAS3	GLIS3	Q8NEA6	452
BCAS3	CHD4	Q14839	446
BCAS3	CHCT1	Q86WR6	445
BCAS3	SLC2A9	Q9NRM0	443
BCAS3	SLC17A1	Q14916	440
BCAS3	CNNM2	Q9H8M5	440
BCAS3	MTA2	O94776	432

IntAct

Human interaction partners of BCAS3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

19 partners by confidence:

Partner	Interaction type	MIscore	Records
PHAF1	physical association	0.660	1
CDC23	physical association	0.560	3
CTBP1	physical association	0.560	3
CTBP2	physical association	0.560	3
PLEKHF2	physical association	0.560	3
VIM	colocalization	0.560	3
ATM	physical association	0.370	1
BAG4	physical association	0.370	1
CCND1	physical association	0.370	1
FBXW7	physical association	0.370	1
KRAS	physical association	0.370	1
PALB2	physical association	0.370	1
PHB1	physical association	0.370	1
PTPN1	physical association	0.370	1
SMAD4	physical association	0.370	1
STK11	physical association	0.370	1
TGFB1	physical association	0.370	1
TSG101	physical association	0.370	1
XRCC3	physical association	0.370	1

BioGRID (111 interactions; top human partners by supporting records): C16orf70 (Two-hybrid; 7 records), ESR1 (Reconstituted Complex; 4 records), PELP1 (Affinity Capture-Western; 4 records), TP53 (Affinity Capture-MS; 4 records), WIPI2 (Affinity Capture-MS; 4 records), DDB1 (Affinity Capture-Western; 3 records), HIST1H3A (Reconstituted Complex; 3 records), DOCK5 (Affinity Capture-MS; 2 records), MAGEE1 (Affinity Capture-MS; 2 records), VWA5A (Affinity Capture-MS; 2 records), APEX1 (Affinity Capture-RNA), ATM (Two-hybrid), BAG4 (Two-hybrid), BAG5 (Affinity Capture-MS), C12orf74 (Affinity Capture-MS)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of cell population proliferation	8	17.7×	3e-06
DNA damage response	5	14.1×	3e-03
positive regulation of gene expression	6	12.2×	1e-03

Disease & clinical

Genetic variants

Variant evidence for BCAS3: 197 ClinVar records (17 pathogenic / likely pathogenic); 114 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	15
Uncertain significance	132
Likely benign	16
Benign	4

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 17 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1687612	NM_017679.5(BCAS3):c.1906C>T (p.Arg636Ter)	Pathogenic	criteria provided, single submitter	1
2664164	NM_017679.5(BCAS3):c.386T>A (p.Leu129Ter)	Likely pathogenic	criteria provided, single submitter	1
3256232	NM_017679.5(BCAS3):c.2425G>T (p.Gly809Cys)	Likely pathogenic	criteria provided, single submitter	1
3376507	NM_017679.5(BCAS3):c.1630C>T (p.Arg544Ter)	Likely pathogenic	criteria provided, single submitter	1
4850709	NM_017679.5(BCAS3):c.1723del (p.Ser575fs)	Likely pathogenic	criteria provided, single submitter	1
4936303	NM_017679.5(BCAS3):c.1762+1G>A	Likely pathogenic	criteria provided, single submitter	1
4936305	NM_017679.5(BCAS3):c.2062C>T (p.Arg688Ter)	Likely pathogenic	criteria provided, single submitter	1
57501	GRCh37/hg19 17q23(chr17:58934659-60395826)x1	Pathogenic	criteria provided, single submitter	1
993272	NM_017679.5(BCAS3):c.2182C>T (p.Gln728Ter)	Likely pathogenic	no assertion criteria provided	1
993273	NM_017679.5(BCAS3):c.1133del (p.Val378fs)	Likely pathogenic	no assertion criteria provided	1
993274	NM_017679.5(BCAS3):c.530del (p.Met177fs)	Likely pathogenic	no assertion criteria provided	1
993276	NM_017679.5(BCAS3):c.2029+4_2029+7del	Likely pathogenic	no assertion criteria provided	1
993277	NM_017679.5(BCAS3):c.2425G>C (p.Gly809Arg)	Likely pathogenic	no assertion criteria provided	1
1048567	NM_017679.5(BCAS3):c.337C>T (p.Gln113Ter)	Likely pathogenic	no assertion criteria provided	1
1048568	NM_017679.5(BCAS3):c.576C>A (p.Cys192Ter)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore BCAS3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 4,419):

Position(s)	Effect	Δscore	Sites
17:60679451–60679452	acceptor_loss	1.0000	5
17:60683971	acceptor_gain	1.0000
17:60684037–60684038	donor_loss	1.0000	4
17:60689684–60689685	acceptor_loss	1.0000	6
17:60747193	acceptor_gain	1.0000
17:60747196–60747197	acceptor_loss	1.0000	6
17:60868574–60868575	acceptor_gain	1.0000	5
17:60868574	acceptor_loss	1.0000
17:60868684–60868685	donor_loss	1.0000	4
17:60874660–60874661	acceptor_loss	1.0000	4

AlphaMissense

2,724 missense substitutions predicted likely pathogenic (of 5,986 scored), across 677 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M740	9	0.992	1.000
M866	9	0.949	0.997
H430	8	0.998	0.999
H446	8	0.995	0.999
F744	8	0.991	1.000
F746	8	0.988	1.000
F39	8	0.987	1.000
D416	8	0.984	0.998
S456	8	0.984	0.999
H346	8	0.982	0.995
F347	8	0.982	0.999
F183	8	0.980	0.999
H731	8	0.980	0.999
H350	8	0.977	0.995
H735	8	0.976	0.998
F359	8	0.975	0.998
N453	8	0.975	0.999
F458	8	0.973	1.000
F432	8	0.970	0.999
F208	8	0.969	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.73e-07

Disease associations

OMIM: gene MIM:607470 | disease phenotypes: MIM:619641

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Hengel-Maroofian-Schols syndrome	Strong	Autosomal recessive	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Hereditary spastic paraplegia, childhood onset	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Fetal anomalies	amber

Mondo (1): Hengel-Maroofian-Schols syndrome (MONDO:0859208)

Orphanet (1): Global developmental delay-intellectual disability-microcephaly-short stature-brain iron accumulation syndrome (Orphanet:697067)

HPO phenotypes

39 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000194	Open mouth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000574	Thick eyebrow
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000687	Widely spaced teeth
HP:0000692	Tooth malposition
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001647	Bicuspid aortic valve
HP:0002059	Cerebral atrophy
HP:0002141	Gait imbalance
HP:0002194	Delayed gross motor development
HP:0002445	Tetraplegia
HP:0002493	Upper motor neuron dysfunction
HP:0002540	Inability to walk
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0008366	Foot joint contracture
HP:0010864	Severe intellectual disability
HP:0011400	Abnormal CNS myelination
HP:0012471	Thick vermilion border
HP:0033725	Thin corpus callosum
HP:0100660	Dyskinesia

GWAS associations

showing 30 of 114 associations:

Study	Trait	p-value
GCST008058_76	Estimated glomerular filtration rate	1e-106
GCST008059_7	Estimated glomerular filtration rate	5e-88
GCST008747_116	Estimated glomerular filtration rate	1e-57
GCST008747_92	Estimated glomerular filtration rate	2e-57
GCST006979_683	Heel bone mineral density	2e-48
GCST007344_76	Estimated glomerular filtration rate	3e-47
GCST008972_26	Urate levels	8e-45
GCST90002384_322	Hemoglobin	1e-36
GCST008058_38	Estimated glomerular filtration rate	2e-36
GCST90002383_376	Hematocrit	8e-36
GCST90002403_126	Red blood cell count	3e-35
GCST010083_51	Hemoglobin levels	4e-33
GCST008745_69	Estimated glomerular filtration rate in non-diabetics	2e-32
GCST006288_559	Heel bone mineral density	2e-31
GCST009462_92	Optic disc size	2e-31
GCST008059_34	Estimated glomerular filtration rate	4e-30
GCST005984_42	Glomerular filtration rate	1e-28
GCST005986_41	Blood urea nitrogen levels	2e-26
GCST007344_15	Estimated glomerular filtration rate	2e-26
GCST005985_57	Creatinine levels	2e-25
GCST008062_116	Blood urea nitrogen levels	2e-23
GCST008972_237	Urate levels	2e-23
GCST008971_77	Urate levels	7e-23
GCST007725_2	Serum uric acid levels	9e-23
GCST007733_36	Serum uric acid levels	9e-23
GCST007431_66	Lung function (FEV1/FVC)	1e-22
GCST003401_24	Glomerular filtration rate in non diabetics (creatinine)	3e-22
GCST003372_58	Glomerular filtration rate (creatinine)	8e-22
GCST010002_354	Refractive error	3e-21
GCST004292_23	Glomerular filtration rate (creatinine)	4e-21

EFO canonical traits (from GWAS)

26 canonical traits:

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0005188	CCL11 measurement
EFO:0004531	urate measurement
EFO:0006897	airway responsiveness measurement
EFO:0004514	bone quantitative ultrasound measurement
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004695	intraocular pressure measurement
EFO:0004838	calcium measurement
EFO:0004761	uric acid measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0009928	Diuretic use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0600003	vitamin C measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007986	reticulocyte count
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

53 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	8
Aflatoxin B1	affects expression, decreases expression, increases methylation	6
bisphenol A	decreases methylation, increases expression, affects cotreatment, decreases expression	4
Air Pollutants	decreases expression, affects cotreatment, increases abundance, affects expression	3
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	3
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	decreases sumoylation	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
bisphenol B	decreases expression	1
bisphenol Z	decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.