PSD2

Summary

PSD2 (pleckstrin and Sec7 domain containing 2, HGNC:19092) is a protein-coding gene on chromosome 5q31.2, encoding PH and SEC7 domain-containing protein 2 (Q9BQI7).

Predicted to enable guanyl-nucleotide exchange factor activity and phospholipid binding activity. Predicted to be involved in regulation of ARF protein signal transduction. Predicted to be located in cleavage furrow and ruffle membrane. Predicted to be active in glutamatergic synapse and postsynapse.

Source: NCBI Gene 84249 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 135 total
• MANE Select transcript: NM_032289

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19092
Approved symbol	PSD2
Name	pleckstrin and Sec7 domain containing 2
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761B0514, EFA6C
Ensembl gene	ENSG00000146005
Ensembl biotype	protein_coding
OMIM	620656
Entrez	84249

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000274710, ENST00000651792, ENST00000859299, ENST00000859300, ENST00000859301, ENST00000937868, ENST00000969647

RefSeq mRNA: 1 — MANE Select: NM_032289 NM_032289

CCDS: CCDS4216

Canonical transcript exons

ENST00000274710 — 15 exons

Exon	Start	End
ENSE00000973442	139814170	139814364
ENSE00000973444	139821893	139822005
ENSE00000973445	139822726	139822784
ENSE00000973446	139833702	139833791
ENSE00000973447	139835723	139835766
ENSE00000973448	139836811	139837001
ENSE00000973451	139838628	139838772
ENSE00000973452	139840027	139840170
ENSE00001038984	139813309	139813758
ENSE00001038985	139837625	139837782
ENSE00001038987	139837168	139837238
ENSE00001260531	139795808	139795975
ENSE00001260542	139842271	139844466
ENSE00001260548	139809391	139809811
ENSE00002525980	139817481	139817561

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 95.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.1896 / max 143.7956, expressed in 141 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58870	3.1563	140
58869	0.0333	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral globus pallidus	UBERON:0002476	95.82	gold quality
caudate nucleus	UBERON:0001873	95.25	gold quality
putamen	UBERON:0001874	94.28	gold quality
right frontal lobe	UBERON:0002810	93.38	gold quality
medial globus pallidus	UBERON:0002477	93.37	gold quality
nucleus accumbens	UBERON:0001882	93.34	gold quality
amygdala	UBERON:0001876	93.12	gold quality
globus pallidus	UBERON:0001875	93.05	gold quality
cortical plate	UBERON:0005343	92.93	gold quality
hypothalamus	UBERON:0001898	92.90	gold quality
primary visual cortex	UBERON:0002436	92.59	gold quality
substantia nigra	UBERON:0002038	92.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.28	gold quality
postcentral gyrus	UBERON:0002581	92.11	gold quality
temporal lobe	UBERON:0001871	92.04	gold quality
anterior cingulate cortex	UBERON:0009835	91.76	gold quality
frontal cortex	UBERON:0001870	91.66	gold quality
frontal lobe	UBERON:0016525	91.66	gold quality
neocortex	UBERON:0001950	91.59	gold quality
midbrain	UBERON:0001891	91.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.54	gold quality
entorhinal cortex	UBERON:0002728	91.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.48	gold quality
cerebral cortex	UBERON:0000956	91.39	gold quality
superior frontal gyrus	UBERON:0002661	91.35	gold quality
prefrontal cortex	UBERON:0000451	91.34	gold quality
Ammon’s horn	UBERON:0001954	91.25	gold quality
parietal lobe	UBERON:0001872	90.42	gold quality
occipital lobe	UBERON:0002021	90.23	gold quality
middle temporal gyrus	UBERON:0002771	90.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting PSD2, 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-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-3924	100.00	72.09	2394
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3934-3P	99.76	65.51	1351

Literature-anchored findings (GeneRIF, showing 2)

• PSD2 may be involved in endolysosomal transport-a process known to be important to development of early onset AD. (PMID:28738127)
• Brain gene expression of PADI2, ZNF385A, PSD2, and A2ML1 and DNA methylation dysregulations are implicated in the alteration of brain tissue properties associated with late-life cognitive decline above and beyond the influence of common neuropathologic conditions. (PMID:29084334)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	psd2	ENSDARG00000063036
mus_musculus	Psd2	ENSMUSG00000024347
rattus_norvegicus	Psd2	ENSRNOG00000019177
drosophila_melanogaster	siz	FBGN0026179
drosophila_melanogaster	Sec71	FBGN0028538
drosophila_melanogaster	garz	FBGN0264560
caenorhabditis_elegans		WBGENE00007703
caenorhabditis_elegans		WBGENE00008685
caenorhabditis_elegans	agef-1	WBGENE00012386

Paralogs (15): CYTH3 (ENSG00000008256), PSD (ENSG00000059915), MON2 (ENSG00000061987), ARFGEF1 (ENSG00000066777), CYTH4 (ENSG00000100055), CYTH2 (ENSG00000105443), GBF1 (ENSG00000107862), CYTH1 (ENSG00000108669), IQSEC3 (ENSG00000120645), ARFGEF2 (ENSG00000124198), IQSEC2 (ENSG00000124313), PSD4 (ENSG00000125637), IQSEC1 (ENSG00000144711), PSD3 (ENSG00000156011), FBXO8 (ENSG00000164117)

Protein

Protein identifiers

PH and SEC7 domain-containing protein 2 — Q9BQI7 (reviewed: Q9BQI7)

Alternative names: Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6 C, Pleckstrin homology and SEC7 domain-containing protein 2

All UniProt accessions (2): A0A494C0U2, Q9BQI7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane. Cell projection. Ruffle membrane. Cleavage furrow.

Similarity. Belongs to the PSD family.

RefSeq proteins (1): NP_115665* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000904	Sec7_dom	Domain
IPR001605	PH_dom-spectrin-type	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR023394	Sec7_C_sf	Homologous_superfamily
IPR035999	Sec7_dom_sf	Homologous_superfamily
IPR041681	PH_9	Domain

Pfam: PF01369, PF15410

UniProt features (19 total): compositionally biased region 5, region of interest 5, sequence variant 3, domain 2, chain 1, transmembrane region 1, modified residue 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQI7-F1	63.18	0.28

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): 191

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, CHANDRAN_METASTASIS_DN, CAGCTG_AP4_Q5, CAGCAGG_MIR370, GOCC_NEURON_PROJECTION, KEGG_ENDOCYTOSIS, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, MODULE_95, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_POSTSYNAPSE, ATGTACA_MIR493, chr5q31

GO Biological Process (1): regulation of ARF protein signal transduction (GO:0032012)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), phospholipid binding (GO:0005543), protein binding (GO:0005515)

GO Cellular Component (9): dendrite (GO:0030425), cleavage furrow (GO:0032154), ruffle membrane (GO:0032587), neuronal cell body (GO:0043025), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synapse	2
ARF protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
lipid binding	1
binding	1
neuron projection	1
dendritic tree	1
cell division site	1
plasma membrane region	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
somatodendritic compartment	1
cell body	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1560 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSD2	PISD	Q9UG56	593
PSD2	ARF6	P26438	510
PSD2	TMEM59L	Q9UK28	474
PSD2	SLC6A5	Q9Y345	451
PSD2	GNG7	O60262	445
PSD2	LLGL1	Q15334	439
PSD2	REEP6	Q96HR9	431
PSD2	RP1L1	Q8IWN7	423
PSD2	SLC45A1	Q9Y2W3	403
PSD2	ANAPC1	Q9H1A4	398
PSD2	SLC6A2	P23975	397
PSD2	NUTM2D	Q5VT03	370
PSD2	M0QZ92	M0QZ92	362
PSD2	IFNG	P01579	349
PSD2	OIP5	O43482	343

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PSD2	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
ANK2	IGKV2-40	psi-mi:“MI:0914”(association)	0.350
PSD2	NMT2	psi-mi:“MI:0914”(association)	0.350
ZBTB49	OTUD4	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): PSD2 (Proximity Label-MS), PSD2 (Affinity Capture-MS), SETD2 (Affinity Capture-MS), UHRF1 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), PSD2 (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), FARP2 (Affinity Capture-MS), FARP1 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), PSD2 (Affinity Capture-MS), PSD2 (Protein-peptide), PSD2 (Affinity Capture-MS), PSD2 (Affinity Capture-MS), PSD2 (Affinity Capture-Western)

ESM2 similar proteins: A0A0G2JUG7, A1L390, E9Q0S6, O08774, O14924, O15085, O43182, O54834, O54960, O60307, O75052, P57095, Q13009, Q3U1V8, Q3U214, Q3UHC7, Q4VAC9, Q5DU25, Q5JU85, Q5RBI7, Q5SXA9, Q5VWQ8, Q60610, Q64512, Q6AX33, Q6DN90, Q6NXJ0, Q6P0Q8, Q6P1I6, Q6ZMN7, Q76G19, Q76LL6, Q76M68, Q7T2V3, Q810W7, Q8CGE9, Q8IX03, Q8R0S2, Q8R4H2, Q8WYP3

Diamond homologs: A0A0G2JUG7, A2A5R2, A5PKW4, D4A631, E1JIT7, F1MUS9, F4IXW2, F4JN05, F4JSZ5, F4K2K3, G3X9K3, G5EET6, O08967, O13690, O13817, O43739, O46382, P11075, P34512, P39993, P47102, P63034, P63035, P97694, P97696, Q10491, Q15438, Q2KI41, Q2PFD7, Q3TES0, Q42510, Q54KA7, Q5DTT2, Q5DU25, Q5E9G6, Q5JU85, Q6DFZ1, Q6DN90, Q6P1I6, Q76M68

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	123
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3058 predictions. Top by Δscore:

Variant	Effect	Δscore
5:139795973:GCG:G	donor_gain	1.0000
5:139795976:G:GG	donor_gain	1.0000
5:139795976:GTGA:G	donor_loss	1.0000
5:139795977:T:A	donor_loss	1.0000
5:139796192:G:GT	donor_gain	1.0000
5:139809385:T:A	acceptor_gain	1.0000
5:139809387:CCAG:C	acceptor_loss	1.0000
5:139809809:GGG:G	donor_gain	1.0000
5:139809809:GGGGT:G	donor_loss	1.0000
5:139809810:GG:G	donor_gain	1.0000
5:139809810:GGG:G	donor_gain	1.0000
5:139809811:GG:G	donor_gain	1.0000
5:139809812:G:GC	donor_loss	1.0000
5:139809812:G:GG	donor_gain	1.0000
5:139809813:T:A	donor_loss	1.0000
5:139813304:CACAG:C	acceptor_loss	1.0000
5:139813306:CAGGT:C	acceptor_loss	1.0000
5:139813307:A:AG	acceptor_gain	1.0000
5:139813308:G:GG	acceptor_gain	1.0000
5:139813453:C:G	donor_gain	1.0000
5:139813521:GGGC:G	donor_gain	1.0000
5:139814168:A:AG	acceptor_gain	1.0000
5:139814169:G:GA	acceptor_gain	1.0000
5:139814361:AGAA:A	donor_gain	1.0000
5:139814362:GAA:G	donor_gain	1.0000
5:139814362:GAAG:G	donor_gain	1.0000
5:139814364:AGTG:A	donor_loss	1.0000
5:139814365:G:C	donor_loss	1.0000
5:139814365:G:GG	donor_gain	1.0000
5:139814369:GT:G	donor_gain	1.0000

AlphaMissense

5076 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:139822759:T:C	L415P	1.000
5:139833733:T:C	F434S	1.000
5:139836971:A:G	K522E	1.000
5:139836973:G:C	K522N	1.000
5:139836973:G:T	K522N	1.000
5:139837188:T:A	W539R	1.000
5:139837188:T:C	W539R	1.000
5:139837189:G:C	W539S	1.000
5:139837190:G:C	W539C	1.000
5:139837190:G:T	W539C	1.000
5:139837210:T:C	L546P	1.000
5:139837743:T:C	L595P	1.000
5:139838650:T:A	W616R	1.000
5:139838650:T:C	W616R	1.000
5:139817512:T:C	Y350H	0.999
5:139817512:T:G	Y350D	0.999
5:139821949:T:A	L385H	0.999
5:139821949:T:C	L385P	0.999
5:139821958:T:C	F388S	0.999
5:139821969:T:G	Y392D	0.999
5:139822741:T:C	L409P	0.999
5:139822749:G:C	A412P	0.999
5:139822750:C:A	A412D	0.999
5:139822753:T:C	L413P	0.999
5:139822762:T:A	L416H	0.999
5:139822762:T:C	L416P	0.999
5:139822766:C:A	N417K	0.999
5:139822766:C:G	N417K	0.999
5:139822774:T:C	L420P	0.999
5:139833718:T:C	M429T	0.999

dbSNP variants (sampled 300 via entrez): RS1000015850 (5:139789923 T>C), RS1000016351 (5:139806279 C>T), RS1000048690 (5:139772029 C>T), RS1000063271 (5:139836275 G>C,T), RS1000065598 (5:139747639 C>A), RS1000102688 (5:139796787 G>A), RS1000134945 (5:139795744 C>T), RS1000140893 (5:139787992 C>A), RS1000158549 (5:139748639 T>C), RS1000182291 (5:139823342 C>T), RS1000215376 (5:139828319 G>A,C,T), RS1000225441 (5:139807563 A>G), RS1000233776 (5:139758655 T>C), RS1000295505 (5:139829303 T>C), RS1000309877 (5:139835792 A>G,T)

Disease associations

OMIM: gene MIM:620656 | 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
GCST005951_151	Body mass index	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
benzo(e)pyrene	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	increases expression	1
Methapyrilene	increases methylation	1
Phenobarbital	increases expression	1
Phthalic Acids	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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