SRGAP2B

Summary

SRGAP2B (SLIT-ROBO Rho GTPase activating protein 2B, HGNC:35237) is a protein-coding gene on chromosome 1q21.1, encoding SLIT-ROBO Rho GTPase-activating protein 2B (P0DMP2). May regulate cell migration and differentiation through interaction with and inhibition of SRGAP2.

This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. This human-specific locus resulted from incomplete segmental duplication of the SLIT-ROBO Rho GTPase activating protein 2 locus. The encoded protein lacks the GTPase activating protein domain compared to proteins encoded by SLIT-ROBO Rho GTPase activating protein 2. The functionality of the protein encoded by this locus has been questioned, as several normal individuals with homozygous deletions for this locus have been identified, and the expression of this locus appears to be much lower than the similar SLIT-ROBO Rho GTPase activating protein 2C (SRGAP2C) locus. The SRGAP2C locus has been shown to encode a protein that functions antagonistically to SLIT-ROBO Rho GTPase activating protein 2 in cortical neuron development.

Source: NCBI Gene 647135 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001271870

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35237
Approved symbol	SRGAP2B
Name	SLIT-ROBO Rho GTPase activating protein 2B
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196369
Ensembl biotype	protein_coding
OMIM	614703
Entrez	647135

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000463366, ENST00000467933, ENST00000494534, ENST00000612199, ENST00000619678, ENST00000621582, ENST00000641863, ENST00000921139, ENST00000921140, ENST00000921141

RefSeq mRNA: 7 — MANE Select: NM_001271870 NM_001271870, NM_001330684, NM_001366280, NM_001368324, NM_001385226, NM_001385227, NM_001385228

CCDS: CCDS72854, CCDS91032

Canonical transcript exons

ENST00000641863 — 10 exons

Exon	Start	End
ENSE00001848190	145092835	145093443
ENSE00001896467	144995008	144995200
ENSE00001933449	144955439	144955601
ENSE00003712932	144914692	144914754
ENSE00003727436	144905859	144906074
ENSE00003733510	144905091	144905219
ENSE00003746592	144893408	144893509
ENSE00003812510	144887288	144892381
ENSE00003813658	144897116	144897340
ENSE00003923687	145095223	145095328

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 99.60.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	99.60	gold quality
sural nerve	UBERON:0015488	96.14	gold quality
cerebellum	UBERON:0002037	95.14	gold quality
cerebellar cortex	UBERON:0002129	95.12	gold quality
cerebellar hemisphere	UBERON:0002245	95.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.08	gold quality
thymus	UBERON:0002370	93.63	gold quality
ventricular zone	UBERON:0003053	90.71	gold quality
adrenal tissue	UBERON:0018303	88.96	gold quality
stromal cell of endometrium	CL:0002255	87.97	gold quality
ganglionic eminence	UBERON:0004023	86.76	gold quality
cortical plate	UBERON:0005343	85.63	gold quality
tibial nerve	UBERON:0001323	85.38	gold quality
spinal cord	UBERON:0002240	85.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.29	gold quality
skin of leg	UBERON:0001511	85.17	gold quality
calcaneal tendon	UBERON:0003701	84.86	gold quality
zone of skin	UBERON:0000014	84.77	gold quality
monocyte	CL:0000576	84.41	gold quality
right lung	UBERON:0002167	84.31	gold quality
skin of abdomen	UBERON:0001416	83.94	gold quality
leukocyte	CL:0000738	83.85	gold quality
placenta	UBERON:0001987	83.49	gold quality
prefrontal cortex	UBERON:0000451	83.04	gold quality
bone marrow cell	CL:0002092	82.96	gold quality
gall bladder	UBERON:0002110	82.43	gold quality
bone marrow	UBERON:0002371	82.37	gold quality
descending thoracic aorta	UBERON:0002345	82.17	gold quality
superior frontal gyrus	UBERON:0002661	81.79	gold quality
Ammon’s horn	UBERON:0001954	81.68	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	47.43
E-CURD-119	yes	32.42
E-HCAD-25	yes	24.09
E-ANND-3	yes	8.00
E-MTAB-7381	no	230.38
E-MTAB-6819	no	210.95
E-MTAB-6524	no	70.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

186 targeting SRGAP2B, 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-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	srgap2	ENSDARG00000032161
mus_musculus	Srgap2	ENSMUSG00000026425
rattus_norvegicus	Srgap2	ENSRNOG00000006733
caenorhabditis_elegans		WBGENE00006406

Paralogs (5): ARHGAP4 (ENSG00000089820), SRGAP2C (ENSG00000171943), SRGAP3 (ENSG00000196220), SRGAP1 (ENSG00000196935), SRGAP2 (ENSG00000266028)

Protein

Protein identifiers

SLIT-ROBO Rho GTPase-activating protein 2B — P0DMP2 (reviewed: P0DMP2)

Alternative names: SLIT-ROBO Rho GTPase activating protein 2 pseudogene 2

All UniProt accessions (4): P0DMP2, A0A087WW56, A0A087X1G6, A0A286YEY3

UniProt curated annotations — full annotation on UniProt →

Function. May regulate cell migration and differentiation through interaction with and inhibition of SRGAP2. In contrast to SRGAP2C, it is not able to induce long-lasting changes in synaptic density throughout adulthood.

Subunit / interactions. May interact with SRGAP2; formation of the heterodimer alters SRGAP2 function.

Miscellaneous. This is one of the 3 duplications of the ancestral gene SRGAP2/SRGAP2A which has undergone human-specific segmental gene duplications. The appearance of SRGAP2B in the human genome is estimated to 3,4 million years. Two larger duplications later copied SRGAP2B to chromosome 1p12 (SRGAP2C) and to proximal 1q21.1 (SRGAP2D). SRGAP2B was identified in some individuals but it is not clear if it produces a functional protein.

RefSeq proteins (7): NP_001258799, NP_001317613, NP_001353209, NP_001355253, NP_001372155, NP_001372156, NP_001372157 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001060	FCH_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR031160	F_BAR_dom	Domain
IPR051627	SLIT-ROBO_RhoGAP	Family

Pfam: PF00611

UniProt features (5 total): chain 1, domain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DMP2-F1	88.76	0.76

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOBP_CELL_JUNCTION_ASSEMBLY, GOCC_NEURON_PROJECTION, chr1q21, GOCC_POSTSYNAPSE, GOCC_NEURON_SPINE, GOCC_SYNAPSE, GOCC_SOMATODENDRITIC_COMPARTMENT

GO Biological Process (3): nervous system development (GO:0007399), negative regulation of cell migration (GO:0030336), regulation of synapse assembly (GO:0051963)

GO Molecular Function (2): GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (2): dendritic spine (GO:0043197), glutamatergic synapse (GO:0098978)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
synapse assembly	1
regulation of synapse organization	1
regulation of cell junction assembly	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
dendrite	1
neuron spine	1
postsynapse	1
synapse	1

Protein interactions and networks

STRING

174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRGAP2B	FAM72D	Q6L9T8	691
SRGAP2B	FAM72C	H0Y354	590
SRGAP2B	FAM72B	Q86X60	589
SRGAP2B	ARHGAP11B	Q3KRB8	575
SRGAP2B	FAM72A	Q5TYM5	411
SRGAP2B	GTF2IRD2	Q86UP8	370
SRGAP2B	GTF2IRD2B	Q6EKJ0	370
SRGAP2B	NOTCH2NLB	P0DPK3	353
SRGAP2B	NBPF15	Q8N660	350
SRGAP2B	NOTCH2NLA	Q7Z3S9	348
SRGAP2B	ARHGAP11A	Q6P4F7	339
SRGAP2B	KCTD19	Q17RG1	338
SRGAP2B	NBPF14	Q5TI25	324
SRGAP2B	IGHV3-11	P01762	296
SRGAP2B	CFAP46	Q8IYW2	290

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CALD1		psi-mi:“MI:0914”(association)	0.350

BioGRID (9): SRGAP2B (Affinity Capture-RNA), SRGAP2B (Two-hybrid), SRGAP2B (Two-hybrid), SRGAP2B (Two-hybrid), SRGAP2B (Two-hybrid), SRGAP2B (Two-hybrid), SRGAP2B (Two-hybrid), ZNF655 (Two-hybrid), SRGAP2B (Affinity Capture-MS)

ESM2 similar proteins: A1XBS5, B0S6J3, D4A208, O35180, O35964, O43295, O75044, P0DJJ0, P0DMP2, P25343, Q08DK5, Q15057, Q1LU86, Q1RMK1, Q2VR06, Q32LM0, Q3SZG6, Q3V2J0, Q5AFE4, Q5FVC7, Q5PPJ9, Q5PPZ5, Q5R8P5, Q5ZIR1, Q5ZJ81, Q5ZK62, Q62419, Q62421, Q68FW8, Q6AYE2, Q6GN09, Q6IVG4, Q6ZQK5, Q6ZTR7, Q7Z6B7, Q812A2, Q8AXU9, Q8BP22, Q8I190, Q8I1C0

Diamond homologs: A0JNB0, A1A5H8, A1Y2K1, A7A261, B0S6J3, B1V8A0, D4A208, F1LM93, F1LXF1, F1RDG9, O35413, O43295, O75044, O94875, P00523, P00525, P05480, P06241, P07947, P09324, P09769, P0DJJ0, P0DMP2, P10936, P11274, P12931, P13115, P13116, P13406, P14084, P14085, P15054, P15882, P19706, P27446, P27447, P30337, P32793, P39688, P42686

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3089 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:144905173:C:G	R250P	1.000
1:144905218:C:G	R235P	1.000
1:144906019:A:G	L181P	1.000
1:144905147:C:G	A259P	0.999
1:144905158:A:G	L255P	0.999
1:144905165:A:C	Y253D	0.999
1:144905176:G:T	A249D	0.999
1:144905177:C:G	A249P	0.999
1:144905208:C:A	K238N	0.999
1:144905208:C:G	K238N	0.999
1:144905210:T:C	K238E	0.999
1:144905219:G:T	R235S	0.999
1:144906011:C:G	A184P	0.999
1:144906023:T:C	K180E	0.999
1:144906032:C:G	A177P	0.999
1:144906062:A:C	Y167D	0.999
1:144914699:A:G	L160P	0.999
1:144995122:A:G	L49P	0.999
1:144995185:A:G	L28P	0.999
1:144897279:G:T	A297D	0.998
1:144897280:C:G	A297P	0.998
1:144897309:A:G	L287P	0.998
1:144905165:A:G	Y253H	0.998
1:144905186:C:G	A246P	0.998
1:144905859:C:A	K234N	0.998
1:144905859:C:G	K234N	0.998
1:144905861:T:C	K234E	0.998
1:144906021:T:A	K180N	0.998
1:144906021:T:G	K180N	0.998
1:144995068:A:G	L67P	0.998

dbSNP variants (sampled 300 via entrez): RS1000594 (1:145060130 A>T), RS1003350 (1:145058288 C>T), RS10127826 (1:145031191 G>A), RS10158906 (1:144959963 C>G,T), RS10159125 (1:145075641 A>T), RS10159129 (1:145075715 A>G,T), RS10217823 (1:145080911 A>G), RS10217824 (1:145080974 A>G), RS10217828 (1:145080910 T>A), RS1028475 (1:145026668 T>C), RS1028476 (1:145026833 C>T), RS10399870 (1:145033419 G>C), RS1040627 (1:144995771 C>A,T), RS1040628 (1:144995885 C>T), RS1040629 (1:144996128 C>T)

Disease associations

OMIM: gene MIM:614703 | 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

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Paraoxon	decreases expression	1
Smoke	decreases expression, increases abundance	1
Valproic Acid	increases expression	1

Clinical trials (associated diseases)

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