FRMPD3

Summary

FRMPD3 (FERM and PDZ domain containing 3, HGNC:29382) is a protein-coding gene on chromosome Xq22.3, encoding FERM and PDZ domain-containing protein 3 (Q5JV73).

This gene encodes a protein that contains a PDZ (post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) domain at the N-terminus followed by a FERM domain. The encoded protein is involved in signal transduction. The PDZ domain is thought to function in protein-protein interactions, mainly by binding to specific C-terminal peptides of other proteins. The FERM domain is found in proteins that are localized to the plasma membrane and are associated with the cytoskeleton.

Source: NCBI Gene 84443 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total — 2 pathogenic
• MANE Select transcript: NM_001388459

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29382
Approved symbol	FRMPD3
Name	FERM and PDZ domain containing 3
Location	Xq22.3
Locus type	gene with protein product
Status	Approved
Aliases	RP5-1070B1.1, KIAA1817
Ensembl gene	ENSG00000147234
Ensembl biotype	protein_coding
OMIM	301005
Entrez	84443

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000276185, ENST00000439554, ENST00000477796, ENST00000683424, ENST00000683843, ENST00000684358

RefSeq mRNA: 3 — MANE Select: NM_001388459 NM_001388459, NM_001388462, NM_032428

CCDS: CCDS94646, CCDS94647

Canonical transcript exons

ENST00000683843 — 15 exons

Exon	Start	End
ENSE00001383947	107554385	107554504
ENSE00001457832	107597321	107598142
ENSE00001457833	107576315	107576459
ENSE00001457834	107564887	107565066
ENSE00001457835	107563111	107563200
ENSE00001457836	107560727	107560853
ENSE00001457838	107560257	107560393
ENSE00001457841	107545737	107545841
ENSE00001457843	107533505	107533550
ENSE00001457845	107530409	107530511
ENSE00001457846	107526582	107526736
ENSE00001739547	107600303	107605251
ENSE00003578076	107550049	107550156
ENSE00003647322	107552795	107552926
ENSE00003919677	107449652	107450005

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 76.56.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.07	gold quality
cerebellar hemisphere	UBERON:0002245	74.94	gold quality
cerebellar cortex	UBERON:0002129	74.88	gold quality
cerebellum	UBERON:0002037	73.93	gold quality
right lobe of thyroid gland	UBERON:0001119	73.06	gold quality
left lobe of thyroid gland	UBERON:0001120	72.37	gold quality
cortical plate	UBERON:0005343	72.16	gold quality
granulocyte	CL:0000094	71.39	gold quality
thyroid gland	UBERON:0002046	71.23	gold quality
hypothalamus	UBERON:0001898	68.91	gold quality
anterior cingulate cortex	UBERON:0009835	67.29	gold quality
endothelial cell	CL:0000115	67.24	silver quality
epithelial cell of pancreas	CL:0000083	66.63	gold quality
kidney epithelium	UBERON:0004819	66.12	gold quality
tibialis anterior	UBERON:0001385	65.83	silver quality
right frontal lobe	UBERON:0002810	65.37	gold quality
prefrontal cortex	UBERON:0000451	65.17	gold quality
right ovary	UBERON:0002118	64.75	gold quality
left ovary	UBERON:0002119	64.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.28	gold quality
neocortex	UBERON:0001950	64.21	gold quality
amygdala	UBERON:0001876	64.01	gold quality
spinal cord	UBERON:0002240	64.00	gold quality
frontal cortex	UBERON:0001870	63.75	gold quality
substantia nigra	UBERON:0002038	63.17	gold quality
Ammon’s horn	UBERON:0001954	63.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	62.89	gold quality
cerebral cortex	UBERON:0000956	62.77	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	62.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting FRMPD3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	frmpd3	ENSDARG00000074865
mus_musculus	Frmpd3	ENSMUSG00000042425
rattus_norvegicus	Frmpd3	ENSRNOG00000065509
drosophila_melanogaster	CG42788	FBGN0261859
caenorhabditis_elegans		WBGENE00001494

Paralogs (2): FRMPD1 (ENSG00000070601), FRMPD4 (ENSG00000169933)

Protein

Protein identifiers

FERM and PDZ domain-containing protein 3 — Q5JV73 (reviewed: Q5JV73)

All UniProt accessions (4): Q5JV73, A0A0A0MSP7, A0A804HJA6, A0A804HKR2

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (3): NP_001375388, NP_001375391, NP_115804 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR001478	PDZ	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR041779	FRMPD1/3/4_FERM_C	Domain
IPR049385	FAK1-like_FERM_C	Domain

Pfam: PF00373, PF00595, PF21477

UniProt features (20 total): compositionally biased region 10, region of interest 7, domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JV73-F1	51.77	0.10

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 53 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOCC_SECRETORY_VESICLE, GOCC_SECRETORY_GRANULE_MEMBRANE, GSE13522_WT_VS_IFNG_KO_SKIN_DN, chrXq22, GOCC_TERTIARY_GRANULE, GOCC_TERTIARY_GRANULE_MEMBRANE, REACTOME_NEUTROPHIL_DEGRANULATION, MIR128_3P, MIR216A_3P, MIR3681_3P, MIR6878_5P, MIR6127, MIR6129

GO Biological Process (0):

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

GO Cellular Component (4): plasma membrane (GO:0005886), secretory granule membrane (GO:0030667), tertiary granule membrane (GO:0070821), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
secretory granule membrane	1
tertiary granule	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FRMPD3	OSGIN2	Q9Y236	456
FRMPD3	OR5T2	Q8NGG2	445
FRMPD3	OR5L2	Q8NGL0	435
FRMPD3	C9orf43	Q8TAL5	405
FRMPD3	TMLHE	Q9NVH6	402
FRMPD3	TMEM132E	Q6IEE7	394
FRMPD3	NXPE2	Q96DL1	379
FRMPD3	PPM1H	Q9ULR3	376
FRMPD3	DLG4	P78352	364
FRMPD3	LIMA1	Q9UHB6	360
FRMPD3	MROH2B	Q7Z745	347
FRMPD3	NPAS4	Q8IUM7	341
FRMPD3	ASB11	Q8WXH4	324
FRMPD3	FLAD1	Q8NFF5	320
FRMPD3	IGSF9B	Q9UPX0	320

IntAct

390 interactions, top by confidence:

A	B	Type	Score
KCNV1	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
USH1C	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
YAP1	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
TBC1D10A	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC15A5	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
WWTR1	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
FRMPD3	E	psi-mi:“MI:0407”(direct interaction)	0.440
NOS1AP	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
PRKN	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
RNF130	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
NECTIN3	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
NRXN3	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
WHRN	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
NECTIN1	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
CREBBP	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
E6	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
Tax	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
PTEN	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
RPS6KA1	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
E	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA1	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
ABRAXAS2	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
ADRB2	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
AGMAT	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (20): FRMPD3 (Affinity Capture-MS), FRMPD3 (Affinity Capture-MS), PKM (Cross-Linking-MS (XL-MS)), FRMPD3 (Cross-Linking-MS (XL-MS)), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS), FRMPD3 (Proximity Label-MS)

ESM2 similar proteins: A0A140LI67, B5KFD7, D4A7V9, M0R4F8, O08774, O35827, O43187, O70167, O70173, O88866, O88900, O95398, O95704, P0C5Y8, Q0P5I2, Q13322, Q14449, Q4QQS0, Q5BIW4, Q5ICW4, Q5JV73, Q5PQS0, Q5R810, Q60760, Q68DX3, Q6IFT4, Q6IRN0, Q6P4K6, Q6REY9, Q6S5L8, Q6TXD4, Q7TSI1, Q80TQ5, Q80VA5, Q8BW88, Q8CFA1, Q8IWE5, Q8R1C9, Q8R2S1, Q8VCC8

Diamond homologs: A2AFR3, A2AKB4, E2QYC9, F1MAD2, O62683, O95049, Q14CM0, Q5JV73, Q5SYB0, Q63ZW7, Q8NI35, Q9QXY1, A1IGU4, A4D2P6, A5PKA5, A8MUH7, D3YZU1, O14745, O15085, Q0QWG9, Q28619, Q3T0X8, Q3UHD6, Q4R6G4, Q5RCF7, Q5T2W1, Q5ZM14, Q60592, Q61085, Q61210, Q6P0Q8, Q6ZM86, Q865P3, Q8K4V4, Q8R4H2, Q8TCX5, Q91XL2, Q92888, Q96L92, Q99MJ6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 192 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
Voltage gated Potassium channels	6	10.7×	2e-03
Assembly and cell surface presentation of NMDA receptors	5	9.3×	6e-03
Adherens junctions interactions	5	9.1×	7e-03
Potassium Channels	9	8.9×	2e-04
RHOQ GTPase cycle	6	8.0×	4e-03
RHOB GTPase cycle	6	6.8×	8e-03
Cardiac conduction	8	6.4×	2e-03
RAC3 GTPase cycle	7	6.1×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of synaptic transmission, glutamatergic	5	17.3×	1e-03
action potential	7	13.9×	3e-04
maintenance of blood-brain barrier	5	13.4×	3e-03
transport across blood-brain barrier	10	10.0×	5e-05
cell-cell adhesion	13	7.3×	4e-05
potassium ion transmembrane transport	9	6.8×	1e-03
protein-containing complex assembly	10	6.3×	1e-03
cell migration	13	4.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	4
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
146845	GRCh38/hg38 Xq21.1-28(chrX:79093152-156003229)x1	Pathogenic
3391958	GRCh37/hg19 Xq21.32-26.1(chrX:92712119-129831493)x1	Pathogenic

SpliceAI

2992 predictions. Top by Δscore:

Variant	Effect	Δscore
X:107530404:TGCA:T	acceptor_loss	1.0000
X:107530406:CA:C	acceptor_loss	1.0000
X:107530508:TCAG:T	donor_loss	1.0000
X:107530509:CAGGT:C	donor_loss	1.0000
X:107530510:AGGTA:A	donor_loss	1.0000
X:107530511:GG:G	donor_loss	1.0000
X:107530512:G:A	donor_loss	1.0000
X:107545735:A:AG	acceptor_gain	1.0000
X:107545736:G:GG	acceptor_gain	1.0000
X:107545736:GTCC:G	acceptor_gain	1.0000
X:107545839:GCA:G	donor_gain	1.0000
X:107545842:G:GG	donor_gain	1.0000
X:107552794:GGAT:G	acceptor_gain	1.0000
X:107552922:CTTAT:C	donor_gain	1.0000
X:107552923:TTAT:T	donor_gain	1.0000
X:107552923:TTATG:T	donor_loss	1.0000
X:107552924:TAT:T	donor_gain	1.0000
X:107552926:TGT:T	donor_loss	1.0000
X:107552927:G:GG	donor_gain	1.0000
X:107552927:G:T	donor_loss	1.0000
X:107552928:TAAG:T	donor_loss	1.0000
X:107554371:T:G	acceptor_gain	1.0000
X:107554375:T:TA	acceptor_gain	1.0000
X:107560255:A:AG	acceptor_gain	1.0000
X:107560256:G:GG	acceptor_gain	1.0000
X:107560256:GA:G	acceptor_gain	1.0000
X:107560389:GTGGA:G	donor_gain	1.0000
X:107560390:TGGA:T	donor_gain	1.0000
X:107560391:GGA:G	donor_gain	1.0000
X:107560391:GGAG:G	donor_gain	1.0000

AlphaMissense

11599 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:107550092:T:C	L182P	1.000
X:107550123:G:C	K192N	1.000
X:107550123:G:T	K192N	1.000
X:107550127:T:C	F194L	1.000
X:107550128:T:C	F194S	1.000
X:107550129:C:A	F194L	1.000
X:107550129:C:G	F194L	1.000
X:107564912:T:C	L414P	1.000
X:107564915:T:C	L415P	1.000
X:107564920:G:A	G417R	1.000
X:107564920:G:C	G417R	1.000
X:107564921:G:A	G417E	1.000
X:107564938:A:C	S423R	1.000
X:107564940:C:A	S423R	1.000
X:107564940:C:G	S423R	1.000
X:107564945:T:A	V425D	1.000
X:107564978:T:C	L436P	1.000
X:107576325:T:C	L469P	1.000
X:107603023:A:C	S1695R	1.000
X:107603025:C:A	S1695R	1.000
X:107603025:C:G	S1695R	1.000
X:107603045:T:C	L1702P	1.000
X:107526689:T:C	F67S	0.999
X:107526719:T:A	V77D	0.999
X:107550089:T:A	V181D	0.999
X:107550098:T:A	V184D	0.999
X:107550104:T:C	L186S	0.999
X:107550121:A:G	K192E	0.999
X:107550133:T:C	F196L	0.999
X:107550134:T:C	F196S	0.999

dbSNP variants (sampled 300 via entrez): RS1000000158 (X:107587149 T>C), RS1000017439 (X:107590176 A>C), RS1000117109 (X:107530174 T>C), RS1000157004 (X:107550140 G>A), RS1000166452 (X:107562296 T>A), RS1000180826 (X:107535501 C>T), RS1000221051 (X:107598199 A>G), RS1000229459 (X:107549670 T>C), RS1000265884 (X:107474618 T>C), RS1000311336 (X:107544640 A>G), RS1000324577 (X:107528601 G>A), RS1000340592 (X:107544170 T>G), RS1000354860 (X:107451909 C>G), RS1000414055 (X:107462175 A>T), RS1000509408 (X:107576718 G>A,C)

Disease associations

OMIM: gene MIM:301005 | 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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Caffeine	decreases phosphorylation	1
Methapyrilene	increases methylation	1

Clinical trials (associated diseases)

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