CBARP

Summary

CBARP (CACN subunit beta associated regulatory protein, HGNC:28617) is a protein-coding gene on chromosome 19p13.3, encoding Voltage-dependent calcium channel beta subunit-associated regulatory protein (Q8N350). Negatively regulates voltage-gated calcium channels by preventing the interaction between their alpha and beta subunits.

Predicted to enable transmembrane transporter binding activity. Predicted to be involved in negative regulation of calcium ion-dependent exocytosis and negative regulation of voltage-gated calcium channel activity. Predicted to be located in growth cone and secretory granule. Predicted to be active in plasma membrane.

Source: NCBI Gene 255057 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 45 total — 1 pathogenic
• GTEx eGene: eQTL in 10 tissues, sQTL in 5 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.11 (unconstrained)
• MANE Select transcript: NM_001393918

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28617
Approved symbol	CBARP
Name	CACN subunit beta associated regulatory protein
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC40084, DOS, BARP
Ensembl gene	ENSG00000099625
Ensembl biotype	protein_coding
Entrez	255057

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 18 nonsense_mediated_decay, 10 protein_coding, 2 retained_intron

MANE Select: ENST00000650044

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

ENST00000650044, ENST00000215376, ENST00000382477, ENST00000589260, ENST00000590083, ENST00000591127, ENST00000648750, ENST00000917007, ENST00000942888, ENST00000942889, ENST00000942890, ENST00001036665, ENST00001036666, ENST00001036667, ENST00001036668, ENST00001036669, ENST00001065767, ENST00001065768, ENST00001065769, ENST00001065770, ENST00001065771, ENST00001065772, ENST00001065773, ENST00001065774, ENST00001065775, ENST00001065776, ENST00001065777, ENST00001065778, ENST00001065779, ENST00001143137

RefSeq mRNA: 2 — MANE Select: NM_001393918 NM_001393918, NM_152769

CCDS: CCDS12057, CCDS92477

Canonical transcript exons

ENST00000650044 — 10 exons

Exon	Start	End
ENSE00000651449	1234191	1234331
ENSE00000795123	1234571	1234742
ENSE00000795124	1235001	1235145
ENSE00000795125	1235779	1235918
ENSE00003575046	1233426	1233636
ENSE00003588315	1231101	1231275
ENSE00003712864	1235501	1235565
ENSE00003832605	1228287	1230142
ENSE00003839343	1235996	1236121
ENSE00003930470	1237756	1238005

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 88.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.6995 / max 138.6809, expressed in 1439 samples.

Highest expression (Bgee): adenohypophysis, nucleus accumbens, pituitary gland, frontal lobe, prefrontal cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CBARP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	4.0e-36	+0.72	19:1233707:G:C
Esophagus Mucosa	eqtl	1.2e-27	-0.91	19:1236397:G:A
Skin Sun Exposed Lower leg	eqtl	3.2e-23	-0.72	19:1236397:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.8e-21	-0.82	19:1236397:G:A
Pituitary	sqtl	6.1e-12	-0.84	19:1233707:G:C
Brain Frontal Cortex BA9	eqtl	9.5e-04	+1.20	19:1026007:C:A
Skin Not Sun Exposed Suprapubic	sqtl	2.9e-03	+0.34	19:1233707:G:C
Brain Nucleus accumbens basal ganglia	sqtl	6.2e-03	+0.57	19:1233707:G:C
Lung	eqtl	8.9e-03	-0.30	19:1531046:G:A
Brain Cortex	eqtl	9.9e-03	+1.17	19:378212:A:G
Nerve Tibial	sqtl	1.0e-02	+1.18	19:661140:C:A
Thyroid	eqtl	1.5e-02	+0.48	19:2040461:G:A
Brain Caudate basal ganglia	eqtl	1.6e-02	+0.13	19:2186238:G:A
Artery Tibial	eqtl	3.0e-02	+0.50	19:868751:C:T
Brain Hippocampus	eqtl	5.0e-02	-0.15	19:285330:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
178000	3.7499	1292
177998	1.6465	492
177999	1.2019	576
177995	0.1012	55

Top tissues by expression

showing 100 of 279 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	88.04	gold quality
nucleus accumbens	UBERON:0001882	86.51	gold quality
pituitary gland	UBERON:0000007	86.45	gold quality
right frontal lobe	UBERON:0002810	85.86	gold quality
prefrontal cortex	UBERON:0000451	84.97	gold quality
caudate nucleus	UBERON:0001873	84.77	gold quality
cingulate cortex	UBERON:0003027	83.51	gold quality
putamen	UBERON:0001874	83.40	gold quality
anterior cingulate cortex	UBERON:0009835	83.36	gold quality
buccal mucosa cell	CL:0002336	83.32	silver quality
cortical plate	UBERON:0005343	83.19	gold quality
neocortex	UBERON:0001950	82.22	gold quality
frontal cortex	UBERON:0001870	82.10	gold quality
frontal lobe	UBERON:0016525	82.07	gold quality
ganglionic eminence	UBERON:0004023	82.03	gold quality
amygdala	UBERON:0001876	81.07	gold quality
sperm	CL:0000019	80.94	silver quality
telencephalon	UBERON:0001893	80.87	gold quality
forebrain	UBERON:0001890	80.79	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.53	gold quality
cerebral cortex	UBERON:0000956	80.47	gold quality
ventricular zone	UBERON:0003053	79.72	gold quality
Ammon’s horn	UBERON:0001954	79.53	gold quality
brain	UBERON:0000955	79.15	gold quality
temporal lobe	UBERON:0001871	78.96	gold quality
central nervous system	UBERON:0001017	78.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.63	gold quality
stromal cell of endometrium	CL:0002255	78.59	gold quality
male germ cell	CL:0000015	78.37	silver quality
primary visual cortex	UBERON:0002436	78.33	gold quality
gingival epithelium	UBERON:0001949	77.98	silver quality
entorhinal cortex	UBERON:0002728	77.69	gold quality
superior frontal gyrus	UBERON:0002661	77.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.14	gold quality
endothelial cell	CL:0000115	77.02	silver quality
Brodmann (1909) area 23	UBERON:0013554	76.00	gold quality
germinal epithelium of ovary	UBERON:0001304	75.60	gold quality
cerebellar cortex	UBERON:0002129	75.10	gold quality
cerebellar hemisphere	UBERON:0002245	75.09	gold quality
postcentral gyrus	UBERON:0002581	75.04	gold quality
hypothalamus	UBERON:0001898	74.65	gold quality
lower esophagus mucosa	UBERON:0035834	74.39	gold quality
medial globus pallidus	UBERON:0002477	74.35	gold quality
occipital lobe	UBERON:0002021	74.34	gold quality
skin of leg	UBERON:0001511	74.15	gold quality
cerebellum	UBERON:0002037	73.85	gold quality
gingiva	UBERON:0001828	73.66	gold quality
parietal lobe	UBERON:0001872	73.47	silver quality
heart right ventricle	UBERON:0002080	73.18	gold quality
middle temporal gyrus	UBERON:0002771	72.52	silver quality
globus pallidus	UBERON:0001875	72.44	gold quality
skin of abdomen	UBERON:0001416	72.40	gold quality
tendon of biceps brachii	UBERON:0008188	71.43	gold quality
zone of skin	UBERON:0000014	71.27	gold quality
substantia nigra	UBERON:0002038	70.65	gold quality
superficial temporal artery	UBERON:0001614	70.44	gold quality
midbrain	UBERON:0001891	70.11	gold quality
lower lobe of lung	UBERON:0008949	69.35	silver quality
embryo	UBERON:0000922	69.05	gold quality
right testis	UBERON:0004534	68.92	gold quality
left testis	UBERON:0004533	68.56	gold quality
testis	UBERON:0000473	67.70	gold quality
oviduct epithelium	UBERON:0004804	67.09	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	67.06	gold quality
ventral tegmental area	UBERON:0002691	66.03	silver quality
esophagus mucosa	UBERON:0002469	65.67	gold quality
cartilage tissue	UBERON:0002418	65.63	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	65.54	gold quality
right atrium auricular region	UBERON:0006631	65.54	gold quality
mucosa of paranasal sinus	UBERON:0005030	65.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	65.31	gold quality
peritoneum	UBERON:0002358	65.24	gold quality
omental fat pad	UBERON:0010414	65.24	gold quality
left adrenal gland cortex	UBERON:0035825	65.05	gold quality
cardiac atrium	UBERON:0002081	64.84	gold quality
adipose tissue of abdominal region	UBERON:0007808	64.80	gold quality
adrenal cortex	UBERON:0001235	64.72	gold quality
cardia of stomach	UBERON:0001162	64.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.63	gold quality
pons	UBERON:0000988	64.59	gold quality
squamous epithelium	UBERON:0006914	64.51	gold quality
dorsal plus ventral thalamus	UBERON:0001897	64.38	silver quality
nipple	UBERON:0002030	64.38	silver quality
spinal cord	UBERON:0002240	64.37	gold quality
saphenous vein	UBERON:0007318	64.32	silver quality
left ovary	UBERON:0002119	64.27	gold quality
ovary	UBERON:0000992	64.22	gold quality
pericardium	UBERON:0002407	64.19	silver quality
superior vestibular nucleus	UBERON:0007227	64.19	silver quality
subthalamic nucleus	UBERON:0001906	64.08	silver quality
esophagus squamous epithelium	UBERON:0006920	63.71	gold quality
renal medulla	UBERON:0000362	63.70	silver quality
medulla oblongata	UBERON:0001896	63.64	silver quality
metanephros cortex	UBERON:0010533	63.64	gold quality
biceps brachii	UBERON:0001507	63.62	gold quality
pylorus	UBERON:0001166	63.60	gold quality
right adrenal gland cortex	UBERON:0035827	63.60	gold quality
vena cava	UBERON:0004087	63.53	gold quality
dorsal root ganglion	UBERON:0000044	63.52	silver quality
vagina	UBERON:0000996	63.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.22

HPA expression

RNA tissue specificity: Group enriched

57 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Frontal cortex	tissue	49.7
Hippocampus	tissue	40.1
Caudate putamen	tissue	37.5
Nucleus accumbens	tissue	31.9
Cerebral cortex	tissue	20.2
Somatosensory cortex	tissue	20.2
Pituitary gland	tissue	19.8
Locus coeruleus	tissue	19.5
Prefrontal cortex	tissue	19.3
Basal ganglia	tissue	19.2
Occipital cortex	tissue	19.1
Temporal cortex	tissue	18.8
Insular cortex	tissue	18.2
Postcentral gyrus	tissue	18.0
Hippocampal formation	tissue	17.9
Entorhinal cortex	tissue	17.9
Motor cortex	tissue	17.1
Cerebellum	tissue	17.1
Retrosplenial and cingulate cortex	tissue	17.1
Retrosplenial cortex	tissue	16.7
Putamen	tissue	15.2
Ventral forebrain	tissue	13.9
Amygdala	tissue	12.5
Septum	tissue	12.2
Olfactory bulb	tissue	12.1
Thalamus	tissue	12.0
Hypothalamus	tissue	11.0
Pons	tissue	10.9
Midbrain	tissue	10.3
Superior colliculi	tissue	9.7
Periaqueductal gray	tissue	8.8
Medulla oblongata	tissue	7.0
Substantia nigra	tissue	6.8
Spinal cord	tissue	5.8
Corpus callosum	tissue	3.4
Choroid plexus	tissue	2.3
Adrenal gland	tissue	1.6
Skin 1	tissue	0.7
Vagina	tissue	0.7
Testis	tissue	0.5
Retina	tissue	0.3
Adipose tissue	tissue	0.3
Stomach 1	tissue	0.2
Endometrium 1	tissue	0.2
Kidney	tissue	0.2
Heart muscle	tissue	0.1
Ovary	tissue	0.1
Seminal vesicle	tissue	0.1
Esophagus	tissue	0.1
Urinary bladder	tissue	0.1
Pancreas	tissue	0.1
Placenta	tissue	0.1
Liver	tissue	0.1
Gallbladder	tissue	0.1
Duodenum	tissue	0.1
Prostate	tissue	0.1
Appendix	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Posterior cingulate cortex (48.9), Hippocampus, CA3 (43.3), Caudate nucleus (37.7), Dentate gyrus (36.9), Hippocampus, CA1 (36.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

20 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-3189-5P	97.55	66.71	655
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-1288-3P	96.86	66.95	536
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-4515	95.70	65.73	716
HSA-MIR-10396B-5P	94.99	63.57	358
HSA-MIR-1908-5P	94.99	63.41	352
HSA-MIR-663A	94.99	63.54	378
HSA-MIR-6727-5P	92.41	61.98	83
HSA-MIR-4258	90.68	62.19	164
HSA-MIR-4508	90.37	59.62	240

Functional genomics

gnomAD constraint: pLI 5.88e-07, LOEUF 1.11, missense Z -2.04 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000650044 — one region, missense o/e 1.17.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbarpb	ENSDARG00000071325
mus_musculus	Cbarp	ENSMUSG00000035640
rattus_norvegicus	Cbarp	ENSRNOG00000024349

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1354170) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased locomotor activity	2
decreased vertical activity	2
increased thigmotaxis	2
decreased body length	1
decreased body weight	1
abnormal social investigation	1
increased anxiety-related response	1
hyperactivity	1
decreased exploration in new environment	1
decreased startle reflex	1
abnormal social/conspecific interaction behavior	1
abnormal bone structure	1
decreased stereotypic behavior	1
abnormal striatum morphology	1
abnormal behavior	1
abnormal spatial working memory	1
increased prepulse inhibition	1
impaired cued conditioning behavior	1
decreased grip strength	1
decreased bone mineral content	1
abnormal synaptic dopamine release	1
abnormal eye anterior chamber depth	1
abnormal response to social novelty	1

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
CBARP-DT	ncRNA	118827813
ATP5F1D	protein-coding	513
MIDN	protein-coding	90007
SBNO2	protein-coding	22904
GPX4	protein-coding	2879
STK11	protein-coding	6794
ARHGAP45	protein-coding	23526
POLR2E	protein-coding	5434

Protein

Protein identifiers

Voltage-dependent calcium channel beta subunit-associated regulatory protein — Q8N350 (reviewed: Q8N350)

All UniProt accessions (4): Q8N350, A0A140LJL2, A0A3B3IRU5, K7ELJ5

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates voltage-gated calcium channels by preventing the interaction between their alpha and beta subunits. Thereby, negatively regulates calcium channels activity at the plasma membrane and indirectly inhibits calcium-regulated exocytosis.

Subunit / interactions. Interacts with voltage-dependent calcium channels CACNB1, CACNB2, CACNB3 and CACNB4 beta subunits; prevents their interaction with the CACNA1C alpha subunit thereby negatively regulating the activity of the corresponding calcium channels.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Cell membrane. Cell projection. Growth cone.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N350-3	1	yes
Q8N350-4	2

RefSeq proteins (2): NP_001380847, NP_689982 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037658	CBARP	Family

Pfam: PF27937

UniProt features (32 total): compositionally biased region 9, modified residue 8, region of interest 6, topological domain 2, splice variant 2, sequence conflict 2, chain 1, transmembrane region 1, glycosylation site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N350-F1	52.23	0.05

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): 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.

Post-translational modifications (8)

Type	Positions
Phosphoserine	299, 304, 507, 528, 621, 699, 703
Phosphothreonine	698

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	29

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: 100 (showing top): MORF_RAGE, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEGATIVE_REGULATION_OF_CALCIUM_ION_DEPENDENT_EXOCYTOSIS, GOBP_REGULATION_OF_VOLTAGE_GATED_CALCIUM_CHANNEL_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_EXOCYTOSIS, GOBP_NEGATIVE_REGULATION_OF_REGULATED_SECRETORY_PATHWAY, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS

GO Biological Process (3): negative regulation of calcium ion-dependent exocytosis (GO:0045955), negative regulation of voltage-gated calcium channel activity (GO:1901386), negative regulation of calcium ion transmembrane transport (GO:1903170)

GO Molecular Function (2): transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), secretory granule (GO:0030141), growth cone (GO:0030426), synaptic vesicle membrane (GO:0030672), cytoplasmic vesicle (GO:0031410)

GO top-level categories

22 GO namespaces:

Category	Terms
calcium-ion regulated exocytosis	1
regulation of calcium ion-dependent exocytosis	1
negative regulation of regulated secretory pathway	1
voltage-gated calcium channel activity	1
negative regulation of calcium ion transmembrane transporter activity	1
regulation of voltage-gated calcium channel activity	1
negative regulation of calcium ion transport	1
calcium ion transmembrane transport	1
regulation of calcium ion transmembrane transport	1
negative regulation of cation transmembrane transport	1
protein binding	1
binding	1
membrane	1
cell periphery	1
endomembrane system	1
secretory vesicle	1
site of polarized growth	1
distal axon	1
synaptic vesicle	1
exocytic vesicle membrane	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

showing 15 of 362 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBARP	FAM174C	Q9BVV8	570
CBARP	CLRN3	Q8NCR9	488
CBARP	BORCS6	Q96GS4	465
CBARP	MIDN	Q504T8	427
CBARP	CRABP2	P29373	400
CBARP	SBNO2	Q9Y2G9	389
CBARP	MGARP	Q8TDB4	385
CBARP	ACTRT3	Q9BYD9	379
CBARP	FSIP2	Q5CZC0	379
CBARP	GHITM	Q9H3K2	370
CBARP	SNAP47	Q5SQN1	362
CBARP	QRICH2	Q9H0J4	361
CBARP	CPLX3	Q8WVH0	359
CBARP	RMDN2	Q96LZ7	345
CBARP	C19orf25	Q9UFG5	343

IntAct

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

3 partners by confidence:

Partner	Interaction type	MIscore	Records
STARD3	physical association	0.590	2
PKM	phosphorylation reaction	0.440	1
BIN1	association	0.350	1

Disease & clinical

Genetic variants

Variant evidence for CBARP: 45 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	33
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 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
60067	GRCh38/hg38 19p13.3(chr19:1156372-1228333)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CBARP’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; 33 predictions of 918):

Position(s)	Effect	Δscore	Sites
19:1231276–1231277	acceptor_loss	1.0000	2
19:1234202	donor_gain	1.0000
19:1234569–1234570	donor_loss	1.0000	5
19:1234743–1234744	acceptor_loss	1.0000	5
19:1234999–1235000	donor_loss	1.0000	3
19:1235777–1235778	donor_loss	1.0000	4
19:1235919–1235920	acceptor_loss	1.0000	6
19:1235923	acceptor_gain	1.0000
19:1236122–1236123	acceptor_loss	1.0000	5
19:1237754	donor_loss	1.0000

AlphaMissense

1,136 missense substitutions predicted likely pathogenic (of 4,516 scored), across 272 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
M501	9	0.968	0.997
D502	8	0.990	0.997
D159	8	0.987	0.997
F160	8	0.987	0.999
D543	8	0.965	0.990
F334	8	0.959	0.995
F134	8	0.956	0.996
D539	8	0.946	0.983
F553	8	0.945	0.997
F550	8	0.940	0.993
H161	8	0.939	0.994
S503	8	0.927	0.997
D436	8	0.924	0.978
S507	8	0.906	0.996
D324	8	0.897	0.968
S322	8	0.887	0.997
H297	8	0.882	0.959
D589	8	0.876	0.929
D547	8	0.871	0.957
D557	8	0.825	0.937

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Disease associations

OMIM: gene `` | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2301759	metformin	Efficacy	Genotype TT is associated with decreased clinical benefit to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes CC + CT.	PMID:39612420

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression, decreases methylation	2
Particulate Matter	increases abundance, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
coumarin	decreases phosphorylation	1
abrine	increases expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Allergens	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Cyclosporine	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

16 trials:

NCT	Phase	Status	Title
NCT03781050	Phase 4	UNKNOWN	Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome
NCT06001476	Phase 4	UNKNOWN	Cold Snare Polypectomy for Small Bowel Polyps in Patients With Peutz-Jeghers Syndrome
NCT02000089	Phase 3	RECRUITING	The Cancer of the Pancreas Screening-5 CAPS5)Study
NCT00811590	Phase 2	TERMINATED	Pilot Study of mTOR Inhibitor Therapy in Peutz-Jeghers Syndrome
NCT01178151	Phase 2	WITHDRAWN	Study of Everolimus in the Treatment of Advanced Malignancies in Patients With Peutz-Jeghers Syndrome
NCT00001452	Not specified	COMPLETED	Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the Carney Complex
NCT00438906	Not specified	COMPLETED	Cancer of the Pancreas Screening Study (CAPS 3)
NCT00633607	Not specified	COMPLETED	Hereditary Colorectal and Associated Tumor Registry Study
NCT02206360	Not specified	COMPLETED	Pancreatic Cancer Early Detection Program
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03806075	Not specified	UNKNOWN	Study of Accurate Diagnosis and Treatment of Peutz-Jeghers Syndrome
NCT04095195	Not specified	RECRUITING	Registry of Subjects at Risk of Pancreatic Cancer
NCT05692596	Not specified	ACTIVE_NOT_RECRUITING	The Pancreas Interception Center (PIC) for Early Detection, Prevention, and Novel Therapeutics
NCT06163365	Not specified	UNKNOWN	Inherited Cancer Early Diagnosis (ICED) Study
NCT06242457	Not specified	COMPLETED	Poorly Differentiated Adenocarcinoma of the Jejunum in a Patient With Peutz-Jeghers Syndrome: A Case Report
NCT06722534	Not specified	RECRUITING	Celecoxib for Prevention of Progression in Peutz-Jeghers Syndrome