RFLNA

Summary

RFLNA (refilin A, HGNC:27051) is a protein-coding gene on chromosome 12q24.31, encoding Refilin-A (Q6ZTI6). Involved in the regulation of the perinuclear actin network and nuclear shape through interaction with filamins.

Predicted to enable filamin binding activity. Predicted to be involved in several processes, including actin filament bundle organization; negative regulation of bone mineralization involved in bone maturation; and negative regulation of chondrocyte development. Predicted to be located in cytoplasm and cytoskeleton. Predicted to be active in actin filament bundle.

Source: NCBI Gene 144347 — RefSeq curated summary.

At a glance

• GWAS associations: 233
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001365156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27051
Approved symbol	RFLNA
Name	refilin A
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ44614, Cfm2, RefilinA
Ensembl gene	ENSG00000178882
Ensembl biotype	protein_coding
OMIM	615927
Entrez	144347

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000324038, ENST00000338359, ENST00000389727, ENST00000545615, ENST00000546355

RefSeq mRNA: 4 — MANE Select: NM_001365156 NM_001204299, NM_001347902, NM_001365156, NM_181709

CCDS: CCDS91768

Canonical transcript exons

ENST00000546355 — 3 exons

Exon	Start	End
ENSE00002299756	124314192	124316024
ENSE00002308323	124295093	124295636
ENSE00003775653	124311818	124311927

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 91.47.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6311 / max 100.0933, expressed in 432 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128613	44.1554	1813
128620	1.1118	318
128621	0.3248	161
206948	0.1945	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	91.47	gold quality
body of stomach	UBERON:0001161	88.72	gold quality
stomach	UBERON:0000945	86.81	gold quality
mucosa of transverse colon	UBERON:0004991	86.67	gold quality
cortical plate	UBERON:0005343	81.69	gold quality
tibial nerve	UBERON:0001323	81.50	gold quality
sural nerve	UBERON:0015488	81.34	gold quality
mucosa of stomach	UBERON:0001199	81.04	gold quality
tibia	UBERON:0000979	79.85	gold quality
transverse colon	UBERON:0001157	79.41	gold quality
rectum	UBERON:0001052	79.07	gold quality
duodenum	UBERON:0002114	78.12	gold quality
colonic mucosa	UBERON:0000317	77.11	gold quality
cartilage tissue	UBERON:0002418	77.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.63	gold quality
endocervix	UBERON:0000458	76.33	gold quality
mucosa of sigmoid colon	UBERON:0004993	76.11	gold quality
ganglionic eminence	UBERON:0004023	76.04	gold quality
fundus of stomach	UBERON:0001160	75.71	gold quality
jejunal mucosa	UBERON:0000399	73.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.70	gold quality
anterior cingulate cortex	UBERON:0009835	73.31	gold quality
small intestine	UBERON:0002108	73.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.67	gold quality
intestine	UBERON:0000160	72.64	gold quality
large intestine	UBERON:0000059	72.48	gold quality
colon	UBERON:0001155	72.42	gold quality
right frontal lobe	UBERON:0002810	71.95	gold quality
cerebellar hemisphere	UBERON:0002245	71.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting RFLNA, 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-302E	99.96	70.74	2669
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4326	98.97	67.63	962

Literature-anchored findings (GeneRIF, showing 2)

• The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative colorectal tumors. (PMID:23490283)
• The present study implies that RFLNA is an additional causative gene for spondylocarpotarsal synostosis syndrome in humans and a defect in forming actin bundles and perinuclear actin caps may be a critical mechanism for the development of spondylocarpotarsal synostosis syndrome. (PMID:30796325)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rflna	ENSDARG00000023484
mus_musculus	Rflna	ENSMUSG00000037962
rattus_norvegicus	Rflna	ENSRNOG00000080603

Paralogs (1): RFLNB (ENSG00000183688)

Protein

Protein identifiers

Refilin-A — Q6ZTI6 (reviewed: Q6ZTI6)

Alternative names: Regulator of filamin protein A

All UniProt accessions (1): Q6ZTI6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of the perinuclear actin network and nuclear shape through interaction with filamins. Plays an essential role in actin cytoskeleton formation in developing cartilaginous cells.

Subunit / interactions. Interacts with FLNA and FLNB.

Subcellular location. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the Refilin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZTI6-1	1	yes
Q6ZTI6-2	2

RefSeq proteins (4): NP_001191228, NP_001334831, NP_001352085, NP_859060 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028215	Refilin	Family

Pfam: PF15068

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZTI6-F1	59.78	0.10

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 (1): 163

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, GOBP_CHONDROCYTE_DEVELOPMENT, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_BONE_MINERALIZATION, GOBP_CHONDROCYTE_DIFFERENTIATION, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_CHONDROCYTE_DIFFERENTIATION, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_DN

GO Biological Process (5): skeletal system morphogenesis (GO:0048705), negative regulation of chondrocyte development (GO:0061182), actin filament bundle organization (GO:0061572), negative regulation of bone mineralization involved in bone maturation (GO:1900158), regulation of chondrocyte development (GO:0061181)

GO Molecular Function (2): filamin binding (GO:0031005), protein binding (GO:0005515)

GO Cellular Component (3): actin filament bundle (GO:0032432), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chondrocyte development	2
cellular anatomical structure	2
skeletal system development	1
animal organ morphogenesis	1
negative regulation of cell development	1
negative regulation of chondrocyte differentiation	1
regulation of chondrocyte development	1
actin filament organization	1
negative regulation of bone mineralization	1
bone mineralization involved in bone maturation	1
regulation of chondrocyte differentiation	1
regulation of cell development	1
cytoskeletal protein binding	1
binding	1
actin filament	1
actin cytoskeleton	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFLNA	FLNB	O75369	595
RFLNA	FLNA	P21333	551
RFLNA	ZNF664	Q8N3J9	543
RFLNA	FLNC	Q14315	507
RFLNA	C17orf67	Q0P5P2	462
RFLNA	ASB7	Q9H672	461
RFLNA	C14orf119	Q9NWQ9	447
RFLNA	PPP4R4	Q6NUP7	442
RFLNA	ZNRD2	O60232	432
RFLNA	GLTP	Q9NZD2	418
RFLNA	CRISPLD1	Q9H336	415
RFLNA	CORO2A	Q92828	414
RFLNA	PLAC9	Q5JTB6	399
RFLNA	TMTC2	Q8N394	398
RFLNA	METTL24	Q5JXM2	395

IntAct

4 interactions, top by confidence:

A	B	Type	Score
RFLNA	FLNA	psi-mi:“MI:0915”(physical association)	0.560
FLNA	RFLNA	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (5): FAM101A (Two-hybrid), FLNA (Two-hybrid), ZNF664-FAM101A (Affinity Capture-RNA), FAM101A (Positive Genetic), FAM101A (Affinity Capture-MS)

ESM2 similar proteins: A3KNX6, A4H824, A4IFN2, A4IGV6, A7E369, B3NY01, B4IL68, B4NU50, B4Q0P1, B4Q0P5, B4R694, M0R5D6, O36399, O88677, P03131, P15130, P18345, P19893, P22484, P24433, P33802, P50615, P50784, P52511, P60571, Q00111, Q1LV19, Q1LY84, Q21733, Q3TEL6, Q567C6, Q5RDK8, Q5SVD0, Q6AXS9, Q6DFB0, Q6IMP4, Q6SWP7, Q6UDF8, Q6ZTI6, Q7TS73

Diamond homologs: Q5SVD0, Q6AXS9, Q6ZTI6, Q7TS73, Q8N5W9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2612 predictions. Top by Δscore:

Variant	Effect	Δscore
12:123974018:CAGGT:C	donor_loss	1.0000
12:123974019:AGG:A	donor_loss	1.0000
12:123974020:GGT:G	donor_loss	1.0000
12:123976224:G:GT	donor_gain	1.0000
12:124289367:TGAGG:T	donor_loss	1.0000
12:124289369:AGGTG:A	donor_loss	1.0000
12:124289371:G:C	donor_loss	1.0000
12:124289372:T:A	donor_loss	1.0000
12:124311816:A:AG	acceptor_gain	1.0000
12:124311817:G:GG	acceptor_gain	1.0000
12:124311817:GCCC:G	acceptor_gain	1.0000
12:124311817:GCCCC:G	acceptor_gain	1.0000
12:124311926:CGGTG:C	donor_loss	1.0000
12:124311928:G:GG	donor_gain	1.0000
12:124311929:T:A	donor_loss	1.0000
12:124314187:TCCA:T	acceptor_loss	1.0000
12:124314190:A:AG	acceptor_gain	1.0000
12:124314190:AGCT:A	acceptor_gain	1.0000
12:124314191:G:GT	acceptor_gain	1.0000
12:124314191:GC:G	acceptor_gain	1.0000
12:124314191:GCT:G	acceptor_gain	1.0000
12:124314191:GCTG:G	acceptor_gain	1.0000
12:124314191:GCTGC:G	acceptor_gain	1.0000
12:123973301:G:T	donor_gain	0.9900
12:123973350:GGA:G	donor_gain	0.9900
12:123973351:GAG:G	donor_gain	0.9900
12:123973353:G:GG	donor_gain	0.9900
12:123974018:CAGG:C	donor_loss	0.9900
12:123974021:GT:G	donor_loss	0.9900
12:123974021:GTA:G	donor_loss	0.9900

AlphaMissense

1400 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:124295502:A:C	S25R	0.991
12:124295504:C:A	S25R	0.991
12:124295504:C:G	S25R	0.991
12:124295526:A:C	S33R	0.988
12:124295528:C:A	S33R	0.988
12:124295528:C:G	S33R	0.988
12:124314325:A:C	S151R	0.988
12:124314327:C:A	S151R	0.988
12:124314327:C:G	S151R	0.988
12:124314314:G:C	R147P	0.986
12:124314313:C:A	R147S	0.982
12:124314364:T:C	F164L	0.982
12:124314366:C:A	F164L	0.982
12:124314366:C:G	F164L	0.982
12:124314454:T:C	F194L	0.981
12:124314456:C:A	F194L	0.981
12:124314456:C:G	F194L	0.981
12:124314385:T:C	F171L	0.977
12:124314387:C:A	F171L	0.977
12:124314387:C:G	F171L	0.977
12:124314229:T:C	F119L	0.973
12:124314231:C:A	F119L	0.973
12:124314231:C:G	F119L	0.973
12:124314332:T:C	L153P	0.973
12:124295508:G:C	D27H	0.965
12:124295515:G:A	G29E	0.963
12:124314266:T:A	V131D	0.963
12:124295514:G:A	G29R	0.961
12:124295514:G:C	G29R	0.961
12:124311881:T:C	F91L	0.961

dbSNP variants (sampled 300 via entrez): RS1000016756 (12:124300329 A>G), RS1000031217 (12:124305210 C>T), RS1000048144 (12:124310723 T>C), RS1000185738 (12:124295462 G>A), RS1000249135 (12:124290142 A>G), RS1000273497 (12:124290699 A>G), RS1000366986 (12:124301281 C>T), RS1000375835 (12:124306431 A>G), RS1000528355 (12:124304922 G>A), RS1000610959 (12:124289434 C>A,T), RS1000676775 (12:124290276 ATATG>A,ATATGTATG), RS1000719569 (12:124313475 G>A), RS1000925112 (12:124300554 G>A), RS1001009989 (12:124309480 C>G,T), RS1001034217 (12:124289295 C>A,T)

Disease associations

OMIM: gene MIM:615927 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

233 associations (top):

Study	Trait	p-value
GCST002647_150	Height	4.000000e-21
GCST002764_12	Optic cup area	2.000000e-07
GCST002764_6	Optic cup area	7.000000e-10
GCST004067_69	Hip circumference adjusted for BMI	2.000000e-08
GCST004075_10	Vertical cup-disc ratio	7.000000e-08
GCST004075_11	Vertical cup-disc ratio	2.000000e-09
GCST004137_22	Optic cup area	4.000000e-10
GCST004137_38	Optic cup area	2.000000e-12
GCST005956_10	Waist-to-hip ratio adjusted for BMI	6.000000e-08
GCST005958_11	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-07
GCST005962_22	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08
GCST006926_5	Osteoarthritis (hip)	3.000000e-09
GCST008839_183	Height	2.000000e-29
GCST009107_2	Body mass index variance	1.000000e-10
GCST009364_56	Triglyceride levels x long total sleep time interaction (2df test)	5.000000e-09
GCST009404_21	Optic cup area	1.000000e-10
GCST009723_71	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2.000000e-09
GCST009724_100	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-14
GCST009846_10	Hallux valgus	4.000000e-06
GCST010241_125	Apolipoprotein A1 levels	2.000000e-33
GCST010242_131	HDL cholesterol levels	1.000000e-12
GCST010244_42	Triglyceride levels	2.000000e-45
GCST010771_1	Osteoarthrosis (time to event)	4.000000e-08
GCST010988_506	Adult body size	2.000000e-10
GCST011331_9	Body mass index and systole blood pressure (pairwise)	2.000000e-08
GCST011334_11	Body mass index and triglycerides (pairwise)	6.000000e-10
GCST011336_13	Body mass index and HDL-C (pairwise)	5.000000e-16
GCST011344_13	Body fat percentage and HDL-C (pairwise)	2.000000e-16
GCST012226_325	Waist circumference adjusted for body mass index	3.000000e-08
GCST012226_326	Waist circumference adjusted for body mass index	5.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0006939	cup-to-disc ratio measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004340	body mass index
EFO:0004530	triglyceride measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004918	age at diagnosis
EFO:0006335	systolic blood pressure
EFO:0007800	body fat percentage
EFO:0007789	BMI-adjusted waist circumference
EFO:0010701	mean reticulocyte volume
EFO:0007986	reticulocyte count

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
Arsenic	affects methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Lead	affects expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Parathion	increases methylation	1
Smoke	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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