CAAP1

Summary

CAAP1 (caspase activity and apoptosis inhibitor 1, HGNC:25834) is a protein-coding gene on chromosome 9p21.2, encoding Caspase activity and apoptosis inhibitor 1 (Q9H8G2). Anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop.

Involved in negative regulation of apoptotic process.

Source: NCBI Gene 79886 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 69 total
• MANE Select transcript: NM_024828

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25834
Approved symbol	CAAP1
Name	caspase activity and apoptosis inhibitor 1
Location	9p21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13657, CAAP
Ensembl gene	ENSG00000120159
Ensembl biotype	protein_coding
Entrez	79886

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000333916, ENST00000483493, ENST00000495958, ENST00000517946, ENST00000520187, ENST00000625311, ENST00000650615, ENST00000903808, ENST00000903809, ENST00000903810, ENST00000924906

RefSeq mRNA: 2 — MANE Select: NM_024828 NM_001167575, NM_024828

CCDS: CCDS55299, CCDS6516

Canonical transcript exons

ENST00000333916 — 6 exons

Exon	Start	End
ENSE00001332177	26840685	26842647
ENSE00001483706	26892413	26892802
ENSE00003528093	26886104	26886188
ENSE00003581341	26884810	26884885
ENSE00003590058	26887313	26887513
ENSE00003647677	26861066	26861139

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 94.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6266 / max 304.3934, expressed in 1801 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100314	14.3802	1783
100313	5.0141	1594
100312	0.8685	493
100311	0.3637	180

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	94.41	gold quality
colonic mucosa	UBERON:0000317	94.22	gold quality
choroid plexus epithelium	UBERON:0003911	93.87	gold quality
corpus epididymis	UBERON:0004359	93.49	gold quality
caput epididymis	UBERON:0004358	92.33	gold quality
secondary oocyte	CL:0000655	91.39	gold quality
jejunal mucosa	UBERON:0000399	91.22	gold quality
pigmented layer of retina	UBERON:0001782	90.53	gold quality
rectum	UBERON:0001052	90.23	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.54	gold quality
oral cavity	UBERON:0000167	89.42	gold quality
ventricular zone	UBERON:0003053	89.37	gold quality
right adrenal gland cortex	UBERON:0035827	88.84	gold quality
bronchial epithelial cell	CL:0002328	88.53	gold quality
adrenal tissue	UBERON:0018303	88.34	gold quality
duodenum	UBERON:0002114	88.23	gold quality
cauda epididymis	UBERON:0004360	87.83	gold quality
palpebral conjunctiva	UBERON:0001812	87.72	gold quality
left adrenal gland	UBERON:0001234	87.56	gold quality
right adrenal gland	UBERON:0001233	87.50	gold quality
adrenal gland	UBERON:0002369	87.42	gold quality
jejunum	UBERON:0002115	87.27	gold quality
superficial temporal artery	UBERON:0001614	87.26	gold quality
adrenal cortex	UBERON:0001235	87.23	gold quality
left adrenal gland cortex	UBERON:0035825	87.00	gold quality
mucosa of transverse colon	UBERON:0004991	86.98	gold quality
nephron tubule	UBERON:0001231	86.85	gold quality
adult organism	UBERON:0007023	86.78	gold quality
liver	UBERON:0002107	86.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.43
E-GEOD-124858	no	85.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting CAAP1, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6835-3P	99.93	70.49	2904

Literature-anchored findings (GeneRIF, showing 4)

• The data suggest that C9orf82 functions as an anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop. It is designated as Conserved Anti-Apoptotic Protein (CAAP). (PMID:21980415)
• MKL1/miR-5100/CAAP1 loop regulates autophagy and apoptosis in gastric cancer cells. (PMID:32315812)
• LncRNA LncOGD-1006 alleviates OGD-induced ischemic brain injury regulating apoptosis through miR-184-5p/CAAP1 axis. (PMID:33336752)
• Proteomic analysis reveals CAAP1 negatively correlates with platinum resistance in ovarian cancer. (PMID:36870674)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	caap1	ENSDARG00000079652
mus_musculus	Caap1	ENSMUSG00000028578
rattus_norvegicus	Caap1	ENSRNOG00000007299
drosophila_melanogaster	CG32176	FBGN0052176
caenorhabditis_elegans		WBGENE00008859

Protein

Protein identifiers

Caspase activity and apoptosis inhibitor 1 — Q9H8G2 (reviewed: Q9H8G2)

Alternative names: Conserved anti-apoptotic protein

All UniProt accessions (4): A0A3B3ISJ3, E5RFV1, E5RFW3, Q9H8G2

UniProt curated annotations — full annotation on UniProt →

Function. Anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop.

Tissue specificity. Ubiquitous.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H8G2-1	1	yes
Q9H8G2-2	2

RefSeq proteins (2): NP_001161047, NP_079104* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038991	CAAP1	Family

Pfam: PF15335

UniProt features (22 total): compositionally biased region 5, modified residue 5, region of interest 4, sequence conflict 3, chain 1, cross-link 1, splice variant 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H8G2-F1	63.18	0.15

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 (6): 89, 90, 120, 203, 312, 104

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): ACATTCC_MIR1_MIR206, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, NUYTTEN_EZH2_TARGETS_DN, MODULE_69, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B, CCGNMNNTNACG_UNKNOWN, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP, MATTHEWS_SKIN_CARCINOGENESIS_VIA_JUN, STEIN_ESRRA_TARGETS_UP, DAVICIONI_MOLECULAR_ARMS_VS_ERMS_UP, HIRSCH_CELLULAR_TRANSFORMATION_SIGNATURE_UP, ESC_V6.5_UP_LATE.V1_DN, ARNT2_TARGET_GENES, DACH1_TARGET_GENES

GO Biological Process (3): apoptotic process (GO:0006915), negative regulation of apoptotic process (GO:0043066), regulation of apoptotic process (GO:0042981)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of programmed cell death	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAAP1	ZSWIM8	A7E2V4	513
CAAP1	GREB1L	Q9C091	460
CAAP1	BFAR	Q9NZS9	450
CAAP1	TMEM244	Q5VVB8	447
CAAP1	SNX13	Q9Y5W8	447
CAAP1	ANGEL2	Q5VTE6	441
CAAP1	PLAA	Q9Y263	416
CAAP1	TRIP11	Q15643	410
CAAP1	SPIRE1	Q08AE8	410
CAAP1	AFTPH	Q6ULP2	391
CAAP1	MIER1	Q8N108	378
CAAP1	TNIP1	Q15025	370
CAAP1	PANO1	I0J062	367
CAAP1	TULP4	Q9NRJ4	362
CAAP1	GADD45GIP1	Q8TAE8	350

IntAct

31 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
CAAP1	E	psi-mi:“MI:0915”(physical association)	0.370
THOC1	TARS3	psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
JMJD6	U2SURP	psi-mi:“MI:0914”(association)	0.350
AKAP17A	NOS1AP	psi-mi:“MI:0914”(association)	0.350
ACTN1	ACTN4	psi-mi:“MI:0914”(association)	0.350
DDX39B	RBM33	psi-mi:“MI:0914”(association)	0.350
RBM33	DDX39A	psi-mi:“MI:0914”(association)	0.350
RBM39	RPS3A	psi-mi:“MI:0914”(association)	0.350
RTCB	MCRIP1	psi-mi:“MI:0914”(association)	0.350
SNRPA	DDX39A	psi-mi:“MI:0914”(association)	0.350
SNRPB	DDX39A	psi-mi:“MI:0914”(association)	0.350
ING5	CCDC85C	psi-mi:“MI:0914”(association)	0.350
AKAP17A	AHCYL1	psi-mi:“MI:0914”(association)	0.350
KLHL28	APOA1	psi-mi:“MI:0914”(association)	0.350
SF3B1	FAM83G	psi-mi:“MI:0914”(association)	0.350
SRSF7	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
NDEL1	CAAP1	psi-mi:“MI:0915”(physical association)	0.000
CAAP1	KAT7	psi-mi:“MI:0915”(physical association)	0.000
CAAP1	PTN	psi-mi:“MI:0915”(physical association)	0.000
CAAP1	XRCC4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (61): CAAP1 (Affinity Capture-MS), CAAP1 (Affinity Capture-MS), CAAP1 (Affinity Capture-MS), CAAP1 (Affinity Capture-MS), CAAP1 (Affinity Capture-MS), CAAP1 (Affinity Capture-MS), CAAP1 (Affinity Capture-MS), CAAP1 (Affinity Capture-MS), CAAP1 (Affinity Capture-MS), CAAP1 (Proximity Label-MS), CAAP1 (Affinity Capture-MS), CAAP1 (Affinity Capture-MS), XRCC4 (Two-hybrid), KAT7 (Two-hybrid), PTN (Two-hybrid)

ESM2 similar proteins: A0JNH9, A1L162, A2VCV0, A6QQ66, B3NLX1, B4P6W7, B8QB46, O75496, O75971, O88513, P32447, P51860, P53911, P85107, Q03563, Q04996, Q2T9W9, Q3UYG8, Q4VA55, Q5H9M0, Q5RD97, Q5W0B1, Q5ZMS4, Q60524, Q641E3, Q65Z40, Q66H73, Q6AWX6, Q6BKL0, Q6DFV7, Q6KAQ7, Q6PG04, Q6TXG9, Q794H2, Q7X9V2, Q7Z5K2, Q8INT5, Q8IW19, Q8IYH5, Q8L7S0

Diamond homologs: Q2T9W9, Q8VDY9, Q9H8G2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA 3’-end processing	5	35.2×	2e-05
mRNA Polyadenylation	7	22.0×	6e-06
mRNA Splicing	5	19.6×	2e-04
Processing of Capped Intron-Containing Pre-mRNA	6	17.6×	5e-05
mRNA Splicing - Major Pathway	7	13.7×	4e-05
Metabolism of RNA	8	11.9×	2e-05
Dengue Virus-Host Interactions	6	9.8×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing	8	20.8×	1e-06
mRNA processing	7	16.2×	3e-05
mRNA splicing, via spliceosome	5	13.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1019 predictions. Top by Δscore:

Variant	Effect	Δscore
9:26842644:TTTC:T	acceptor_gain	1.0000
9:26842645:TTC:T	acceptor_gain	1.0000
9:26842646:TCC:T	acceptor_loss	1.0000
9:26842648:CTGT:C	acceptor_loss	1.0000
9:26842655:C:CT	acceptor_gain	1.0000
9:26842655:C:T	acceptor_gain	1.0000
9:26842656:A:T	acceptor_gain	1.0000
9:26861060:TCATA:T	donor_loss	1.0000
9:26861061:CATAC:C	donor_loss	1.0000
9:26861062:ATAC:A	donor_loss	1.0000
9:26861063:TA:T	donor_loss	1.0000
9:26861064:A:C	donor_loss	1.0000
9:26861065:C:G	donor_loss	1.0000
9:26861135:CTTGC:C	acceptor_gain	1.0000
9:26861136:TTGCC:T	acceptor_loss	1.0000
9:26861137:TGCCT:T	acceptor_loss	1.0000
9:26861140:C:CC	acceptor_gain	1.0000
9:26861140:CT:C	acceptor_loss	1.0000
9:26861141:T:C	acceptor_loss	1.0000
9:26884808:A:AC	donor_gain	1.0000
9:26884809:C:CG	donor_gain	1.0000
9:26884809:CT:C	donor_gain	1.0000
9:26884809:CTG:C	donor_gain	1.0000
9:26884809:CTGA:C	donor_gain	1.0000
9:26884812:A:AC	donor_gain	1.0000
9:26884813:C:CC	donor_gain	1.0000
9:26884813:CTGA:C	donor_gain	1.0000
9:26884883:CACCT:C	acceptor_gain	1.0000
9:26884887:T:C	acceptor_gain	1.0000
9:26886102:AC:A	donor_gain	1.0000

AlphaMissense

2395 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:26842335:A:G	L351P	1.000
9:26842339:C:G	A350P	1.000
9:26842344:A:C	I348S	1.000
9:26842344:A:G	I348T	1.000
9:26842344:A:T	I348N	1.000
9:26842348:C:G	A347P	1.000
9:26842354:C:G	A345P	1.000
9:26842355:C:A	R344S	1.000
9:26842355:C:G	R344S	1.000
9:26842356:C:A	R344M	1.000
9:26842359:A:C	M343R	1.000
9:26842359:A:G	M343T	1.000
9:26842365:A:G	L341P	1.000
9:26842365:A:T	L341H	1.000
9:26842371:A:G	L339P	1.000
9:26842374:A:G	L338P	1.000
9:26887329:A:G	L163P	1.000
9:26842332:A:G	M352T	0.999
9:26842340:T:A	K349N	0.999
9:26842340:T:G	K349N	0.999
9:26842349:T:A	R346S	0.999
9:26842349:T:G	R346S	0.999
9:26842350:C:G	R346T	0.999
9:26842356:C:G	R344T	0.999
9:26842357:T:C	R344G	0.999
9:26842358:C:A	M343I	0.999
9:26842358:C:G	M343I	0.999
9:26842358:C:T	M343I	0.999
9:26842359:A:T	M343K	0.999
9:26842361:C:A	E342D	0.999

dbSNP variants (sampled 300 via entrez): RS1000009285 (9:26892005 A>T), RS1000020392 (9:26850467 C>G), RS1000040166 (9:26861410 T>G), RS1000117647 (9:26884895 G>A,C), RS1000138460 (9:26867077 C>G,T), RS1000193038 (9:26840364 A>G), RS1000220852 (9:26881339 G>A), RS1000289089 (9:26845971 C>A,T), RS1000292793 (9:26881139 T>A,C), RS1000322952 (9:26850661 C>T), RS1000487761 (9:26856125 A>G,T), RS1000508455 (9:26882550 G>A,T), RS1000549953 (9:26865511 A>G,T), RS1000578886 (9:26845062 G>A), RS1000580726 (9:26887587 G>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003025_16	Attention function in attention deficit hyperactive disorder	6.000000e-06
GCST003771_16	Loneliness	5.000000e-06
GCST004068_35	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	1.000000e-06
GCST004797_7	Brain volume in infants (grey matter)	6.000000e-07
GCST009028_16	Adverse response to drug	1.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007636	attention function measurement
EFO:0007865	loneliness measurement
EFO:0008368	infant grey matter volume measurement
EFO:0009658	adverse effect

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
beauvericin	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
buprofezin	decreases expression	1
abrine	increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases phosphorylation	1
Thiram	decreases expression	1
Vitamin E	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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