CARMIL3

Summary

CARMIL3 (capping protein regulator and myosin 1 linker 3, HGNC:20272) is a protein-coding gene on chromosome 14q11.2, encoding Capping protein, Arp2/3 and myosin-I linker protein 3 (Q8ND23).

Predicted to be involved in cell migration and regulation of Arp2/3 complex-mediated actin nucleation. Located in cytoplasm and plasma membrane.

Source: NCBI Gene 90668 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_138360

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20272
Approved symbol	CARMIL3
Name	capping protein regulator and myosin 1 linker 3
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	BC008134, crml-1
Ensembl gene	ENSG00000186648
Ensembl biotype	protein_coding
OMIM	614716
Entrez	90668

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 retained_intron

ENST00000342740, ENST00000559694, ENST00000560349, ENST00000561354, ENST00000873684, ENST00000873685, ENST00000969240

RefSeq mRNA: 1 — MANE Select: NM_138360 NM_138360

CCDS: CCDS32054

Canonical transcript exons

ENST00000342740 — 40 exons

Exon	Start	End
ENSE00001493206	24065622	24065750
ENSE00002543641	24052009	24052193
ENSE00002572301	24069379	24069729
ENSE00003459381	24054088	24054138
ENSE00003462944	24063120	24063183
ENSE00003469907	24059135	24059189
ENSE00003471036	24055237	24055310
ENSE00003476487	24069137	24069247
ENSE00003477428	24053709	24053803
ENSE00003477531	24057960	24058064
ENSE00003487296	24060628	24060756
ENSE00003505844	24059664	24059732
ENSE00003508614	24058680	24058761
ENSE00003511364	24057167	24057244
ENSE00003513560	24064958	24065273
ENSE00003518928	24054396	24054511
ENSE00003528798	24068786	24068966
ENSE00003530803	24059270	24059442
ENSE00003533887	24061497	24061672
ENSE00003550923	24056622	24056708
ENSE00003552772	24058890	24058986
ENSE00003555607	24055701	24055789
ENSE00003558727	24060927	24061040
ENSE00003560583	24068584	24068702
ENSE00003561373	24054242	24054301
ENSE00003577565	24062480	24062567
ENSE00003591134	24054711	24054808
ENSE00003613397	24066398	24066464
ENSE00003630570	24056915	24057024
ENSE00003640407	24062709	24062846
ENSE00003640916	24063325	24063533
ENSE00003649232	24066567	24066656
ENSE00003649586	24055066	24055136
ENSE00003650824	24057803	24057879
ENSE00003654262	24064246	24064346
ENSE00003655616	24058155	24058224
ENSE00003662024	24056299	24056393
ENSE00003667090	24055543	24055618
ENSE00003667721	24060157	24060255
ENSE00003692822	24059970	24060063

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 94.37.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3590 / max 85.4042, expressed in 377 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138965	1.3590	377

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	94.37	gold quality
cerebellar hemisphere	UBERON:0002245	94.16	gold quality
cerebellar cortex	UBERON:0002129	94.13	gold quality
cerebellum	UBERON:0002037	94.11	gold quality
cortical plate	UBERON:0005343	91.54	gold quality
pituitary gland	UBERON:0000007	84.54	gold quality
adenohypophysis	UBERON:0002196	81.84	gold quality
hypothalamus	UBERON:0001898	81.27	gold quality
granulocyte	CL:0000094	80.94	gold quality
ganglionic eminence	UBERON:0004023	80.61	gold quality
right frontal lobe	UBERON:0002810	80.39	gold quality
brain	UBERON:0000955	79.59	gold quality
superior frontal gyrus	UBERON:0002661	78.37	gold quality
anterior cingulate cortex	UBERON:0009835	78.24	gold quality
frontal cortex	UBERON:0001870	77.84	gold quality
Ammon’s horn	UBERON:0001954	77.33	gold quality
cerebral cortex	UBERON:0000956	77.25	gold quality
primary visual cortex	UBERON:0002436	76.81	gold quality
temporal lobe	UBERON:0001871	76.66	gold quality
amygdala	UBERON:0001876	76.56	gold quality
prefrontal cortex	UBERON:0000451	76.12	gold quality
substantia nigra	UBERON:0002038	75.81	gold quality
skin of abdomen	UBERON:0001416	75.75	gold quality
zone of skin	UBERON:0000014	75.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.64	gold quality
skin of leg	UBERON:0001511	75.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.59	gold quality
nucleus accumbens	UBERON:0001882	75.58	gold quality
putamen	UBERON:0001874	74.24	gold quality
caudate nucleus	UBERON:0001873	73.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting CARMIL3, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-340-3P	98.11	68.25	679
HSA-MIR-6827-3P	98.08	72.27	651
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-2114-5P	96.00	64.56	617
HSA-MIR-381-5P	91.91	65.03	65

Literature-anchored findings (GeneRIF, showing 2)

• a novel oncofetal-like gene, LRRC16B, was indentified. (PMID:21102520)
• Capping Protein Regulator and Myosin 1 Linker 3 Is Required for Tumor Metastasis. (PMID:31694931)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	carmil3	ENSDARG00000086990
mus_musculus	Carmil3	ENSMUSG00000022211
rattus_norvegicus	Carmil3	ENSRNOG00000025518
drosophila_melanogaster	LRR	FBGN0033212
caenorhabditis_elegans	crml-1	WBGENE00010641

Paralogs (4): RNH1 (ENSG00000023191), CARMIL1 (ENSG00000079691), PPP1R37 (ENSG00000104866), CARMIL2 (ENSG00000159753)

Protein

Protein identifiers

Capping protein, Arp2/3 and myosin-I linker protein 3 — Q8ND23 (reviewed: Q8ND23)

Alternative names: Capping protein regulator and myosin 1 linker protein 3, Leucine-rich repeat-containing protein 16B

All UniProt accessions (1): Q8ND23

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Widely expressed, with much higher levels in fetal tissues than in adult ones. Up-regulated in certain cancer tissues.

Domain organisation. The C-terminus is necessary for localization to the cell membrane.

Similarity. Belongs to the CARMIL family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8ND23-1	1	yes
Q8ND23-2	2
Q8ND23-3	3

RefSeq proteins (1): NP_612369* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR031943	CARMIL_C	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR041245	CARMIL_PH	Domain
IPR051279	PP1-Reg/Actin-Interact_Protein	Family

Pfam: PF13516, PF16000, PF17888

UniProt features (32 total): repeat 10, compositionally biased region 9, region of interest 5, splice variant 5, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8ND23-F1	64.77	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, CATRRAGC_UNKNOWN, GOBP_CELL_JUNCTION_ORGANIZATION, RGTTAMWNATT_HNF1_01, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY, BRN2_01, GOBP_ACTIN_FILAMENT_ORGANIZATION, KMCATNNWGGA_UNKNOWN, GATA1_01, GOBP_REGULATION_OF_ARP2_3_COMPLEX_MEDIATED_ACTIN_NUCLEATION

GO Biological Process (3): cell migration (GO:0016477), regulation of Arp2/3 complex-mediated actin nucleation (GO:0034315), regulation of postsynapse assembly (GO:0150052)

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

GO Cellular Component (6): cytoplasm (GO:0005737), plasma membrane (GO:0005886), lamellipodium (GO:0030027), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synapse	2
cell motility	1
Arp2/3 complex-mediated actin nucleation	1
regulation of actin nucleation	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell leading edge	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CARMIL3	TMOD4	Q9NZQ9	588
CARMIL3	SRGAP2	O75044	512
CARMIL3	TMEM145	Q8NBT3	509
CARMIL3	ZBBX	A8MT70	447
CARMIL3	RUNDC3A	Q59EK9	422
CARMIL3	FAM110C	Q1W6H9	421
CARMIL3	WASHC2C	Q9Y4E1	400
CARMIL3	KIAA0408	Q6ZU52	370
CARMIL3	A6NDT3	A6NDT3	364
CARMIL3	SRGAP3	O43295	361
CARMIL3	MAP6D1	Q9H9H5	357
CARMIL3	TMEM151A	Q8N4L1	356
CARMIL3	MTCL3	Q5TF21	353
CARMIL3	PAXBP1	Q9Y5B6	348
CARMIL3	MAP10	Q9P2G4	348

IntAct

2 interactions, top by confidence:

A	B	Type	Score
E7	COPE	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): LRRC16B (Synthetic Lethality), LRRC16B (Affinity Capture-MS), LRRC16B (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2VDW6, A4D2P6, A8VU90, B0BNK9, E9PY61, F1LQY6, O94810, O95382, Q05AA6, Q0QWG9, Q13474, Q2TBQ9, Q3KR56, Q3UFQ8, Q3UR97, Q3V3V9, Q5FVC2, Q5R8E2, Q5XHY1, Q60875, Q61085, Q6F5E8, Q6P597, Q6P5Z2, Q6PRD1, Q6V7V2, Q80XL1, Q80ZJ8, Q865S3, Q86UD0, Q8C6B2, Q8K031, Q8K045, Q8N4Y2, Q8ND23, Q91W40, Q91ZP9, Q92502, Q92974, Q969H4

Diamond homologs: Q3UFQ8, Q3V3V9, Q5VZK9, Q5XHY1, Q6EDY6, Q6F5E8, Q8ND23, Q54G18, A6QLE5, B0FPE9, D9I2F9, D9I2G1, D9I2G3, D9I2H0, P10775, P13489, P29315, P59045, P59046, Q288C4, Q3TKR3, Q66X01, Q66X03, Q66X05, Q66X19, Q66X22, Q6B966, Q7RTR0, Q86W24, Q86W25, Q8BU40, Q8C6J9, Q8HZP9, Q8R4B8, Q8WX94, Q91VI7, Q96MN2, Q96P20, Q9C000, Q9NX02

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5429 predictions. Top by Δscore:

Variant	Effect	Δscore
14:24053704:CTCA:C	acceptor_loss	1.0000
14:24053705:TCA:T	acceptor_loss	1.0000
14:24053706:CAGA:C	acceptor_loss	1.0000
14:24053707:A:AG	acceptor_gain	1.0000
14:24053707:AGACA:A	acceptor_loss	1.0000
14:24053708:G:GG	acceptor_gain	1.0000
14:24053800:GCTG:G	donor_gain	1.0000
14:24053801:CTGG:C	donor_loss	1.0000
14:24053803:GGTGA:G	donor_loss	1.0000
14:24053804:G:GA	donor_loss	1.0000
14:24053805:T:A	donor_loss	1.0000
14:24054085:TA:T	acceptor_loss	1.0000
14:24054236:TCCTA:T	acceptor_loss	1.0000
14:24054237:CCTA:C	acceptor_loss	1.0000
14:24054238:CTAGG:C	acceptor_loss	1.0000
14:24054239:TA:T	acceptor_loss	1.0000
14:24054241:G:A	acceptor_loss	1.0000
14:24054297:ATCAG:A	donor_gain	1.0000
14:24054298:TCAG:T	donor_gain	1.0000
14:24054298:TCAGG:T	donor_loss	1.0000
14:24054299:CAG:C	donor_gain	1.0000
14:24054300:AG:A	donor_gain	1.0000
14:24054301:GG:G	donor_gain	1.0000
14:24054302:G:GG	donor_gain	1.0000
14:24054392:CCA:C	acceptor_loss	1.0000
14:24054393:CAG:C	acceptor_loss	1.0000
14:24054394:A:AG	acceptor_gain	1.0000
14:24054394:A:AT	acceptor_loss	1.0000
14:24054395:G:GA	acceptor_gain	1.0000
14:24054395:GA:G	acceptor_gain	1.0000

AlphaMissense

8898 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:24054104:G:C	R51P	1.000
14:24054806:G:A	C153Y	1.000
14:24055071:T:C	F156L	1.000
14:24055072:T:C	F156S	1.000
14:24055073:C:A	F156L	1.000
14:24055073:C:G	F156L	1.000
14:24055083:T:G	Y160D	1.000
14:24055134:T:A	W177R	1.000
14:24055134:T:C	W177R	1.000
14:24055136:G:C	W177C	1.000
14:24055136:G:T	W177C	1.000
14:24055237:G:C	D178H	1.000
14:24055238:A:C	D178A	1.000
14:24055238:A:G	D178G	1.000
14:24055250:T:A	I182N	1.000
14:24055252:T:G	Y183D	1.000
14:24055277:T:C	F191S	1.000
14:24055291:T:C	F196L	1.000
14:24055292:T:C	F196S	1.000
14:24055293:C:A	F196L	1.000
14:24055293:C:G	F196L	1.000
14:24055579:C:A	N214K	1.000
14:24055579:C:G	N214K	1.000
14:24055586:T:C	F217L	1.000
14:24055587:T:C	F217S	1.000
14:24055588:C:A	F217L	1.000
14:24055588:C:G	F217L	1.000
14:24055762:T:C	L248P	1.000
14:24058760:T:A	N491K	1.000
14:24058760:T:G	N491K	1.000

dbSNP variants (sampled 300 via entrez): RS1000063852 (14:24062143 C>G), RS1000122181 (14:24050612 A>C), RS1000516122 (14:24054402 G>A,T), RS1000518143 (14:24061867 G>A), RS1000736951 (14:24062784 C>T), RS1000843039 (14:24067086 A>G), RS1000863100 (14:24055499 A>G,T), RS1000874263 (14:24066770 A>C,G), RS1001487361 (14:24051374 C>G), RS1001518403 (14:24051128 G>C,T), RS1001745221 (14:24056303 T>G), RS1001820888 (14:24050198 TTC>T), RS1001865236 (14:24056831 C>T), RS1001875197 (14:24056543 G>A), RS1002165370 (14:24069859 T>A)

Disease associations

OMIM: gene MIM:614716 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
Aflatoxin B1	decreases methylation	2
GSK-J4	increases expression	1
ethylbenzene	decreases methylation, increases expression, affects cotreatment	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
clothianidin	increases expression	1
abrine	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases methylation, increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Toluene	decreases methylation, increases expression, affects cotreatment	1
Urethane	increases expression	1
Xylenes	decreases methylation, increases expression, affects cotreatment	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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