CRACD

Summary

CRACD (capping protein inhibiting regulator of actin dynamics, HGNC:29219) is a protein-coding gene on chromosome 4q12, encoding Capping protein-inhibiting regulator of actin dynamics (Q6ZU35). Involved in epithelial cell integrity by acting on the maintenance of the actin cytoskeleton.

Involved in negative regulation of barbed-end actin filament capping. Predicted to be located in cytosol.

Source: NCBI Gene 57482 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 248 total
• MANE Select transcript: NM_001393381

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29219
Approved symbol	CRACD
Name	capping protein inhibiting regulator of actin dynamics
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	CRAD
Ensembl gene	ENSG00000109265
Ensembl biotype	protein_coding
OMIM	618327
Entrez	57482

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000264229, ENST00000503618, ENST00000504228, ENST00000505410, ENST00000514330, ENST00000541073, ENST00000629263, ENST00000636006, ENST00000646253, ENST00000682029, ENST00000891237, ENST00000891238

RefSeq mRNA: 6 — MANE Select: NM_001393381 NM_001393381, NM_001393382, NM_001393383, NM_001393384, NM_001393385, NM_020722

CCDS: CCDS43230

Canonical transcript exons

ENST00000682029 — 11 exons

Exon	Start	End
ENSE00000716911	56324104	56324266
ENSE00001147459	56314040	56316689
ENSE00001488076	56313197	56313379
ENSE00001488079	56307535	56307699
ENSE00001556509	56272321	56272492
ENSE00001564369	56179284	56179430
ENSE00003246599	56323377	56323567
ENSE00003483083	56310666	56310734
ENSE00003562187	56298214	56298349
ENSE00003767404	56049098	56049299
ENSE00003916818	56327644	56330609

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 97.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5481 / max 323.1124, expressed in 1095 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47710	6.2620	1093
47716	0.1055	10
47712	0.0456	13
47714	0.0373	3
47711	0.0322	10
47720	0.0223	4
47715	0.0119	5
47718	0.0086	4
47717	0.0076	3
47713	0.0056	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.18	gold quality
sperm	CL:0000019	97.11	gold quality
cortical plate	UBERON:0005343	96.45	gold quality
embryo	UBERON:0000922	94.91	gold quality
ganglionic eminence	UBERON:0004023	94.91	gold quality
jejunal mucosa	UBERON:0000399	94.11	gold quality
ventricular zone	UBERON:0003053	89.84	gold quality
colonic mucosa	UBERON:0000317	89.82	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.43	gold quality
corpus epididymis	UBERON:0004359	87.46	gold quality
left testis	UBERON:0004533	86.94	gold quality
right testis	UBERON:0004534	86.76	gold quality
testis	UBERON:0000473	86.28	gold quality
epithelial cell of pancreas	CL:0000083	86.21	silver quality
adult organism	UBERON:0007023	85.62	gold quality
duodenum	UBERON:0002114	84.73	gold quality
pons	UBERON:0000988	84.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.67	gold quality
gall bladder	UBERON:0002110	81.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.70	gold quality
sural nerve	UBERON:0015488	79.70	gold quality
rectum	UBERON:0001052	78.40	gold quality
pigmented layer of retina	UBERON:0001782	78.29	gold quality
buccal mucosa cell	CL:0002336	75.48	gold quality
prefrontal cortex	UBERON:0000451	74.95	gold quality
entorhinal cortex	UBERON:0002728	74.93	gold quality
smooth muscle tissue	UBERON:0001135	74.24	gold quality
cartilage tissue	UBERON:0002418	74.18	gold quality
superior vestibular nucleus	UBERON:0007227	73.96	gold quality
islet of Langerhans	UBERON:0000006	73.94	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	77.95
E-HCAD-25	yes	39.69
E-ANND-3	yes	5.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

175 targeting CRACD, 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-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-128-3P	99.95	71.17	2484

Literature-anchored findings (GeneRIF, showing 5)

• CRAD (Cancer-related Regulator of Actin Dynamics, previously KIAA1211) binds to and inhibits capping proteins, which leads to actin polymerization. CRAD is ubiquitously expressed in epithelial cells and is required for the maintenance of epithelial cell integrity. Genetic ablation of this gene deregulates Wnt signaling and induces the development of tumors in mouse models. (PMID:30361697)
• Datam indicate that cancer-related regulator of actin dynamics (CRAD) as frequently mutated or transcriptionally downregulated and as a tumour suppressor in colorectal cancer (CRC). (PMID:30361697)
• The overall survival of small cell lung cancer patients carrying KIAA1211 mutation was significantly longer than those with wild-type KIAA1211. (PMID:31699089)
• Knockdown of CRAD suppresses the growth and promotes the apoptosis of human lung cancer cells via Claudin 4. (PMID:33006362)
• Substrate rigidity dictates colorectal tumorigenic cell stemness and metastasis via CRAD-dependent mechanotransduction. (PMID:35172140)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cracd	ENSDARG00000011602
mus_musculus	Cracd	ENSMUSG00000036377
rattus_norvegicus	Cracd	ENSRNOG00000002139

Protein

Protein identifiers

Capping protein-inhibiting regulator of actin dynamics — Q6ZU35 (reviewed: Q6ZU35)

Alternative names: Cancer-related regulator of actin dynamics

All UniProt accessions (7): Q6ZU35, A0A0D9SFJ2, A0A1B0GWF1, A0A2R8Y5Y4, A0A2R8Y6P1, F5H1N7, R4GNI9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in epithelial cell integrity by acting on the maintenance of the actin cytoskeleton. Positively regulates the actin polymerization, by inhibiting the interaction of actin-capping proteins with actin.

Subunit / interactions. Directly interacts with actin-capping proteins CAPZA1, CAPZA2 and CAPZB; this interaction decreases the binding of capping proteins to actin.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed in intestinal epithelial cells (at protein level).

Disease relevance. In colorectal cancers, CRACD gene is observed to be often the target of inactivating mutations. In the absence of genetic mutations, expression levels tend to be down-regulated.

RefSeq proteins (6): NP_001380310, NP_001380311, NP_001380312, NP_001380313, NP_001380314, NP_065773 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028030	DUF4592	Domain
IPR052853	Actin_dynamics_regulator	Family

Pfam: PF15262

UniProt features (50 total): compositionally biased region 24, modified residue 9, region of interest 8, sequence variant 5, sequence conflict 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZU35-F1	55.09	0.08

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 (9): 7, 28, 132, 420, 556, 559, 971, 975, 1017

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_DIGESTION, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ACTIN_FILAMENT_ORGANIZATION

GO Biological Process (4): epithelial structure maintenance (GO:0010669), maintenance of gastrointestinal epithelium (GO:0030277), positive regulation of actin filament polymerization (GO:0030838), negative regulation of barbed-end actin filament capping (GO:2000813)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
tissue homeostasis	1
epithelial structure maintenance	1
digestive system process	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
positive regulation of actin filament depolymerization	1
positive regulation of actin filament polymerization	1
barbed-end actin filament capping	1
negative regulation of cellular component organization	1
regulation of barbed-end actin filament capping	1
binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1019 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRACD	RNF157	Q96PX1	548
CRACD	CDH12	P55289	411
CRACD	MAPK8	P45983	406
CRACD	PABIR3	Q6P4D5	401
CRACD	BORCS8	Q96FH0	392
CRACD	PRPSAP1	Q14558	387
CRACD	FAM13A	O94988	379
CRACD	COL22A1	Q8NFW1	377
CRACD	ARL9	Q6T311	375
CRACD	TMEM51	Q9NW97	367
CRACD	TMEM98	Q9Y2Y6	348
CRACD	XKRX	Q6PP77	346
CRACD	ARMCX6	Q7L4S7	346
CRACD	PDE4DIP	Q5VU43	334
CRACD	ETV3L	Q6ZN32	333

IntAct

28 interactions, top by confidence:

A	B	Type	Score
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
GLI1	TP53	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
VMP1	TPM3	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.350
CTDP1	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PDLIM1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
CALML3	MYO1C	psi-mi:“MI:0914”(association)	0.350
PRPS2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
CRACD	CAPZA1	psi-mi:“MI:0914”(association)	0.350
PXDN	TRAF7	psi-mi:“MI:0914”(association)	0.350
EZR	EEF2K	psi-mi:“MI:2364”(proximity)	0.270
EZR	PLS3	psi-mi:“MI:2364”(proximity)	0.270
EZR	PDLIM1	psi-mi:“MI:2364”(proximity)	0.270
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (53): KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), KIAA1211 (Proximity Label-MS), KIAA1211 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZM56, A2AG50, A2AI08, A2AJI0, A5D7K1, D4A4L4, E1C2Q8, F1LR10, O00515, O14529, O75128, O88573, O88735, P51825, P57016, Q14244, Q32LQ1, Q3KQU3, Q3U2K0, Q5JTD0, Q5NBX1, Q5PR69, Q5R7F9, Q5XHX2, Q5ZIA2, Q5ZJJ1, Q68DK7, Q6IPM2, Q6NV74, Q6NZF1, Q6PDH0, Q6PDM1, Q6PG95, Q6ZU35, Q86UU1, Q8CCJ4, Q8K124, Q8N7J2, Q8TD55, Q96PV7

Diamond homologs: Q5PR69, Q5RG44, Q6NV74, Q6ZU35

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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
Sensory processing of sound by inner hair cells of the cochlea	5	37.1×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	229
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2024 predictions. Top by Δscore:

Variant	Effect	Δscore
4:56179282:A:AG	acceptor_gain	1.0000
4:56179283:G:GG	acceptor_gain	1.0000
4:56179426:GATAG:G	donor_gain	1.0000
4:56179427:A:G	donor_gain	1.0000
4:56272312:A:AG	acceptor_gain	1.0000
4:56272489:TAAG:T	donor_loss	1.0000
4:56272490:AAGGT:A	donor_loss	1.0000
4:56272491:AGGTA:A	donor_loss	1.0000
4:56272492:GGTA:G	donor_loss	1.0000
4:56272493:GTAAT:G	donor_loss	1.0000
4:56272494:T:G	donor_loss	1.0000
4:56307533:A:AG	acceptor_gain	1.0000
4:56307534:G:GA	acceptor_gain	1.0000
4:56307534:GC:G	acceptor_gain	1.0000
4:56307534:GCA:G	acceptor_gain	1.0000
4:56307534:GCAA:G	acceptor_gain	1.0000
4:56307534:GCAAC:G	acceptor_gain	1.0000
4:56307695:ACAAG:A	donor_gain	1.0000
4:56307696:CAAG:C	donor_gain	1.0000
4:56307697:AAG:A	donor_gain	1.0000
4:56307698:AG:A	donor_gain	1.0000
4:56307698:AGGT:A	donor_loss	1.0000
4:56307699:GG:G	donor_gain	1.0000
4:56307700:G:GG	donor_gain	1.0000
4:56307700:GTA:G	donor_loss	1.0000
4:56310664:A:AG	acceptor_gain	1.0000
4:56310665:G:GA	acceptor_gain	1.0000
4:56313193:ACAG:A	acceptor_gain	1.0000
4:56313194:CAGG:C	acceptor_loss	1.0000
4:56313195:A:AC	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000888 (4:56254679 C>T), RS1000016538 (4:56295969 A>G), RS1000017200 (4:56302751 C>T), RS10000186 (4:56213176 A>G), RS1000023443 (4:56181032 G>A), RS1000025939 (4:56171466 T>C), RS1000028335 (4:56132329 C>T), RS1000032477 (4:56161543 C>A), RS10000461 (4:56112213 T>C), RS1000069907 (4:56213929 A>T), RS1000073705 (4:56213679 G>C), RS1000080585 (4:56265105 A>G), RS1000083225 (4:56294205 TGAC>T), RS1000084263 (4:56307862 C>T), RS1000096326 (4:56123798 C>G)

Disease associations

OMIM: gene MIM:618327 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012330_1	HDL levels x SSRI levels interaction in schizophrenia or bipolar disorder	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005658	response to selective serotonin reuptake inhibitor

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	3
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	increases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects methylation	1
Cisplatin	decreases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Hydrogen Peroxide	increases expression	1
Lead	affects splicing	1
Lipopolysaccharides	affects response to substance, increases expression	1
Ozone	increases abundance, affects cotreatment, increases oxidation	1
Quercetin	decreases expression	1

Clinical trials (associated diseases)

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