NRXN3

Protein identityUniProt · HPA

UniProt accession

Q9Y4C0

Gene

NRXN3

Ensembl

ENSG00000021645

Chromosome

14

Canonical length

1643 aa

Protein class

Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

This gene encodes a member of a family of proteins that function in the nervous system as receptors and cell adhesion molecules. Extensive alternative splicing and the use of alternative promoters results in multiple transcript variants and protein isoforms for this gene, but the full-length nature of many of these variants has not been determined. Transcripts that initiate from an upstream promoter encode alpha isoforms, which contain epidermal growth factor-like (EGF-like) sequences and laminin G domains. Transcripts initiating from the downstream promoter encode beta isoforms, which lack EGF-like sequences. Genetic variation at this locus has been associated with a range of behavioral phenotypes, including alcohol dependence and autism spectrum disorder. [provided by RefSeq, Dec 2012]

Canonical amino-acid sequenceUniProt

1643 residues, UniProt reviewed canonical sequence.

>Q9Y4C0|NRXN3
     1  MSSTLHSVFF TLKVSILLGS LLGLCLGLEF MGLPNQWARY LRWDASTRSD LSFQFKTNVS
    61  TGLLLYLDDG GVCDFLCLSL VDGRVQLRFS MDCAETAVLS NKQVNDSSWH FLMVSRDRLR
   121  TVLMLDGEGQ SGELQPQRPY MDVVSDLFLG GVPTDIRPSA LTLDGVQAMP GFKGLILDLK
   181  YGNSEPRLLG SRGVQMDAEG PCGERPCENG GICFLLDGHP TCDCSTTGYG GKLCSEDVSQ
   241  DPGLSHLMMS EQAREENVAT FRGSEYLCYD LSQNPIQSSS DEITLSFKTW QRNGLILHTG
   301  KSADYVNLAL KDGAVSLVIN LGSGAFEAIV EPVNGKFNDN AWHDVKVTRN LRQVTISVDG
   361  ILTTTGYTQE DYTMLGSDDF FYVGGSPSTA DLPGSPVSNN FMGCLKEVVY KNNDIRLELS
   421  RLARIADTKM KIYGEVVFKC ENVATLDPIN FETPEAYISL PKWNTKRMGS ISFDFRTTEP
   481  NGLILFTHGK PQERKDARSQ KNTKVDFFAV ELLDGNLYLL LDMGSGTIKV KATQKKANDG
   541  EWYHVDIQRD GRSGTISVNS RRTPFTASGE SEILDLEGDM YLGGLPENRA GLILPTELWT
   601  AMLNYGYVGC IRDLFIDGRS KNIRQLAEMQ NAAGVKSSCS RMSAKQCDSY PCKNNAVCKD
   661  GWNRFICDCT GTGYWGRTCE REASILSYDG SMYMKIIMPM VMHTEAEDVS FRFMSQRAYG
   721  LLVATTSRDS ADTLRLELDG GRVKLMVNLD CIRINCNSSK GPETLYAGQK LNDNEWHTVR
   781  VVRRGKSLKL TVDDDVAEGT MVGDHTRLEF HNIETGIMTE KRYISVVPSS FIGHLQSLMF
   841  NGLLYIDLCK NGDIDYCELK ARFGLRNIIA DPVTFKTKSS YLSLATLQAY TSMHLFFQFK
   901  TTSPDGFILF NSGDGNDFIA VELVKGYIHY VFDLGNGPNV IKGNSDRPLN DNQWHNVVIT
   961  RDNSNTHSLK VDTKVVTQVI NGAKNLDLKG DLYMAGLAQG MYSNLPKLVA SRDGFQGCLA
  1021  SVDLNGRLPD LINDALHRSG QIERGCEGPS TTCQEDSCAN QGVCMQQWEG FTCDCSMTSY
  1081  SGNQCNDPGA TYIFGKSGGL ILYTWPANDR PSTRSDRLAV GFSTTVKDGI LVRIDSAPGL
  1141  GDFLQLHIEQ GKIGVVFNIG TVDISIKEER TPVNDGKYHV VRFTRNGGNA TLQVDNWPVN
  1201  EHYPTGRQLT IFNTQAQIAI GGKDKGRLFQ GQLSGLYYDG LKVLNMAAEN NPNIKINGSV
  1261  RLVGEVPSIL GTTQTTSMPP EMSTTVMETT TTMATTTTRK NRSTASIQPT SDDLVSSAEC
  1321  SSDDEDFVEC EPSTTGGELV IPLLVEDPLA TPPIATRAPS ITLPPTFRPL LTIIETTKDS
  1381  LSMTSEAGLP CLSDQGSDGC DDDGLVISGY GSGETFDSNL PPTDDEDFYT TFSLVTDKSL
  1441  STSIFEGGYK AHAPKWESKD FRPNKVSETS RTTTTSLSPE LIRFTASSSS GMVPKLPAGK
  1501  MNNRDLKPQP DIVLLPLPTA YELDSTKLKS PLITSPMFRN VPTANPTEPG IRRVPGASEV
  1561  IRESSSTTGM VVGIVAAAAL CILILLYAMY KYRNRDEGSY QVDETRNYIS NSAQSNGTLM
  1621  KEKQQSSKSG HKKQKNKDRE YYV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NRXN3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

124 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NRXN3.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 218 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Short stature
• Relative macrocephaly

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.11

gnomAD pLI

1

gnomAD missense Z

3.44

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult behavior
• axon guidance
• learning
• neuron cell-cell adhesion
• social behavior
• vocalization behavior

Molecular functions

• cell adhesion molecule binding
• metal ion binding
• neuroligin family protein binding
• signaling receptor activity

Cellular components

• plasma membrane
• presynaptic membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• Laminin G domain
• Neurexin/syndecan/glycophorin C
• Concanavalin A-like lectin/glucanase domain superfamily
• Syndecan/Neurexin domain
• Neurexin-related cell adhesion and synaptic protein
• Syndecan domain
• Laminin G domain

KeywordsUniProt

• Alternative promoter usage
• Calcium
• Cell adhesion
• Cell membrane
• Cell projection
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Heparan sulfate
• Membrane
• Metal-binding
• Proteoglycan
• Repeat
• Signal
• Synapse
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of NRXN3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLSTN3
• NLGN2
• NLGN3
• NLGN1