CAPS2

Summary

CAPS2 (calcyphosine 2, HGNC:16471) is a protein-coding gene on chromosome 12q21.1-q21.2, encoding Calcyphosin-2 (Q9BXY5).

Calcyphosine-2 is a calcium-binding protein with 2 EF-hand motifs (Wang et al., 2002 [PubMed 11846421]).

Source: NCBI Gene 84698 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability (Limited, GenCC)
• Clinical variants (ClinVar): 145 total
• MANE Select transcript: NM_001355024

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16471
Approved symbol	CAPS2
Name	calcyphosine 2
Location	12q21.1-q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000180881
Ensembl biotype	protein_coding
OMIM	607724
Entrez	84698

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 20 protein_coding, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000328705, ENST00000336815, ENST00000393284, ENST00000409004, ENST00000409445, ENST00000409799, ENST00000436898, ENST00000486196, ENST00000493070, ENST00000547320, ENST00000548035, ENST00000548958, ENST00000551829, ENST00000552497, ENST00000699294, ENST00000891113, ENST00000891114, ENST00000891115, ENST00000891116, ENST00000891117, ENST00000891118, ENST00000891119, ENST00000891120, ENST00000891121, ENST00000912723, ENST00000968428, ENST00000968429, ENST00000968430, ENST00000968431

RefSeq mRNA: 12 — MANE Select: NM_001355024 NM_001286547, NM_001286548, NM_001355023, NM_001355024, NM_001355025, NM_001355026, NM_001355027, NM_001355030, NM_001355031, NM_001355032, NM_001355033, NM_032606

CCDS: CCDS91727

Canonical transcript exons

ENST00000699294 — 17 exons

Exon	Start	End
ENSE00001356677	75275979	75279065
ENSE00003463742	75323177	75323222
ENSE00003466214	75312848	75312915
ENSE00003488182	75316312	75316434
ENSE00003504878	75284961	75285080
ENSE00003529352	75304757	75304876
ENSE00003536626	75282251	75282347
ENSE00003559516	75321400	75321576
ENSE00003585308	75325239	75325288
ENSE00003611228	75289621	75289775
ENSE00003624673	75298687	75298780
ENSE00003635413	75298871	75298966
ENSE00003637043	75299837	75299911
ENSE00003639214	75291744	75291820
ENSE00003650414	75326418	75326527
ENSE00003663001	75293249	75293367
ENSE00003976185	75329867	75330324

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 96.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.6125 / max 108.5483, expressed in 962 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132160	2.1753	877
132159	0.4148	180
132158	0.0224	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	96.72	gold quality
right uterine tube	UBERON:0001302	95.57	gold quality
bronchus	UBERON:0002185	95.35	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.38	gold quality
calcaneal tendon	UBERON:0003701	91.03	gold quality
caput epididymis	UBERON:0004358	88.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.73	gold quality
corpus callosum	UBERON:0002336	86.14	gold quality
cerebellar hemisphere	UBERON:0002245	84.95	gold quality
cerebellar cortex	UBERON:0002129	84.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.74	gold quality
apex of heart	UBERON:0002098	84.03	gold quality
cerebellum	UBERON:0002037	83.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.69	gold quality
adrenal tissue	UBERON:0018303	83.39	gold quality
adenohypophysis	UBERON:0002196	83.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.22	gold quality
right frontal lobe	UBERON:0002810	83.05	gold quality
pituitary gland	UBERON:0000007	82.74	gold quality
right atrium auricular region	UBERON:0006631	82.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.54	gold quality
hypothalamus	UBERON:0001898	82.25	gold quality
mucosa of stomach	UBERON:0001199	81.99	gold quality
gastrocnemius	UBERON:0001388	81.80	gold quality
muscle of leg	UBERON:0001383	81.76	gold quality
descending thoracic aorta	UBERON:0002345	81.69	gold quality
left ovary	UBERON:0002119	81.54	gold quality
right adrenal gland cortex	UBERON:0035827	81.45	gold quality
anterior cingulate cortex	UBERON:0009835	81.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting CAPS2, 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-4503	99.85	71.45	1869
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4724-3P	97.57	67.31	785
HSA-MIR-383-5P	96.86	67.55	820
HSA-MIR-518E-3P	82.28	65.75	57

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	caps2	ENSDARG00000058486
mus_musculus	Caps2	ENSMUSG00000035694
rattus_norvegicus	Caps2	ENSRNOG00000026600
drosophila_melanogaster	TpnC47D	FBGN0010423
drosophila_melanogaster	TpnC73F	FBGN0010424
drosophila_melanogaster	TpnC41C	FBGN0013348

Paralogs (5): CAPS (ENSG00000105519), PHF24 (ENSG00000122733), CAPSL (ENSG00000152611), EFCAB6 (ENSG00000186976), SPATA21 (ENSG00000187144)

Protein

Protein identifiers

Calcyphosin-2 — Q9BXY5 (reviewed: Q9BXY5)

Alternative names: Calcyphosine-2

All UniProt accessions (7): B9A061, Q9BXY5, C9J524, F8VWP7, F8VZC3, F8W927, H7BXT1

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Abundantly expressed in many tissues. Expressed in brain, colon, heart, kidney, liver, lung, liver, pancreas, placenta, skeletal muscle, testis and thymus. Highest expression in colon, testis, lung, placenta and brain.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BXY5-1	1	yes
Q9BXY5-2	2
Q9BXY5-3	3
Q9BXY5-4	4
Q9BXY5-5	5

RefSeq proteins (12): NP_001273476, NP_001273477, NP_001341952, NP_001341953, NP_001341954, NP_001341955, NP_001341956, NP_001341959, NP_001341960, NP_001341961, NP_001341962, NP_115995 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR051581	Ca-bind	Family
IPR057461	CAYP2_PH	Domain

Pfam: PF13499, PF25348

UniProt features (25 total): binding site 12, splice variant 4, domain 3, sequence conflict 2, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXY5-F1	70.30	0.33

Functional residue map

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

Ligand- & substrate-binding residues (12): 479; 481; 486; 511; 513; 515; 517; 522; 439; 443; 450; 477

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_NEUROGENESIS, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, GOBP_CEREBRAL_CORTEX_NEURON_DIFFERENTIATION, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_HIPPOCAMPUS_DEVELOPMENT, chr12q21, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTRASPECIES_INTERACTION_BETWEEN_ORGANISMS, GOBP_PALLIUM_DEVELOPMENT, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, GOBP_SECRETION

GO Biological Process (0):

GO Molecular Function (2): calcium ion binding (GO:0005509), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	1
cation binding	1

Protein interactions and networks

STRING

701 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPS2	KISS1R	Q969F8	430
CAPS2	KISS1	Q15726	371
CAPS2	CAPS	Q13938	355
CAPS2	TMEM19	Q96HH6	348
CAPS2	ANO9	A1A5B4	347
CAPS2	VAV3	Q9UKW4	324
CAPS2	SERGEF	Q9UGK8	323
CAPS2	SAAL1	Q96ER3	323
CAPS2	DOCK10	Q96BY6	318
CAPS2	GTF2H1	P32780	268
CAPS2	CAVIN1	Q6NZI2	255
CAPS2	SWAP70	Q9UH65	253
CAPS2	DEF6	Q9H4E7	253
CAPS2	PKP3	Q9Y446	253
CAPS2	FIBIN	Q8TAL6	244

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A087WRI3, A0A1B0GTJ6, A0A1B0GUX0, A0A3Q1LFK7, A2BFC9, A2RRW4, A4QMS7, A6NJV1, A6NL82, A6QPC0, A8E5W8, A8QW39, A9JS51, B9EJX3, E1B9R1, E1BNS6, F1P3Y5, H3BRN8, Q0VB26, Q2T9Q3, Q2TA11, Q32L72, Q4KKZ1, Q4QR77, Q4R5Y0, Q5NC57, Q5PQN4, Q5RC32, Q5XI56, Q5ZMW6, Q6J272, Q6ZN84, Q6ZQR2, Q6ZVS7, Q8BUG5, Q8N1D5, Q8N6G2, Q8N865, Q8TC05, Q8WW14

Diamond homologs: Q4R8T1, Q5RE62, Q5THR3, Q6P1E8, Q9BXY5, Q09665, P80363, Q8BUG5, Q9GKR6, B0G159, P10463, P41150, Q0VCC0, Q13938, Q6P8Y1, Q8WWF8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	116
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:75298907:A:G	L324P	0.985
12:75298934:C:T	G315E	0.985
12:75298710:A:C	Y360D	0.983
12:75299857:A:C	F297L	0.981
12:75299857:A:T	F297L	0.981
12:75299859:A:G	F297L	0.981
12:75299858:A:G	F297S	0.980
12:75298889:C:G	R330P	0.977
12:75298935:C:G	G315R	0.977
12:75298935:C:T	G315R	0.977
12:75298935:C:A	G315W	0.974
12:75298940:A:G	L313P	0.974
12:75284965:C:G	R523P	0.972
12:75284979:C:A	R518S	0.971
12:75284979:C:G	R518S	0.971
12:75282342:A:C	F526L	0.970
12:75282342:A:T	F526L	0.970
12:75282344:A:G	F526L	0.970
12:75293288:C:G	R394P	0.970
12:75298882:A:C	F332L	0.969
12:75298882:A:T	F332L	0.969
12:75298884:A:G	F332L	0.969
12:75298924:G:C	F318L	0.968
12:75298924:G:T	F318L	0.968
12:75298926:A:G	F318L	0.968
12:75293357:A:G	L371S	0.967
12:75298709:T:G	Y360S	0.967
12:75298911:A:G	S323P	0.967
12:75284968:A:T	V522D	0.965
12:75312881:A:T	V228D	0.965

dbSNP variants (sampled 300 via entrez): RS1000007801 (12:75316957 G>A), RS1000025624 (12:75297953 C>T), RS1000026613 (12:75387317 T>C), RS1000030049 (12:75347022 T>A), RS1000056925 (12:75332455 C>G), RS1000063783 (12:75303495 C>G), RS1000080217 (12:75346637 C>A,T), RS1000173902 (12:75372589 C>T), RS1000184559 (12:75277475 A>C), RS1000195627 (12:75303823 G>A), RS1000212181 (12:75329233 G>A), RS1000219512 (12:75350123 T>C), RS1000232902 (12:75373018 G>A), RS1000266789 (12:75286355 T>A), RS1000267298 (12:75372822 T>C)

Disease associations

OMIM: gene MIM:607724 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability	Limited	Autosomal recessive

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	3
bisphenol A	affects cotreatment, increases expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders