GJC2 (gap junction protein gamma 2)

Gene

• Entrez ID: 57165
• Gene name: Gap junction protein gamma 2
• Gene symbol: GJC2
• Synonyms: CX46.6, Cx47, GJA12, HLD2, LMPH1C, LMPHM3, PMLDAR, SPG44
• Chromosome: 1
• Chromosome location: 1q42.13
• Summary: This gene encodes a gap junction protein. Gap junction proteins are members of a large family of homologous connexins and comprise 4 transmembrane, 2 extracellular, and 3 cytoplasmic domains. This gene plays a key role in central myelination and is involv

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs74315311	T>C	Pathogenic	Missense variant, coding sequence variant
rs74315312	C>T	Pathogenic	Missense variant, coding sequence variant
rs74315313	C>T	Pathogenic	Stop gained, coding sequence variant
rs74315314	T>C,G	Pathogenic	Missense variant, coding sequence variant
rs75469429	C>A,G,T	Benign, pathogenic, benign-likely-benign	Missense variant, coding sequence variant, synonymous variant
rs267606846	C>T	Pathogenic	Missense variant, coding sequence variant
rs267606847	C>T	Pathogenic	Missense variant, coding sequence variant
rs375318012	C>G,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs397514734	G>A	Pathogenic	Coding sequence variant, missense variant
rs587776888	A>G	Pathogenic	Upstream transcript variant
rs587777496	A>G	Pathogenic	Upstream transcript variant
rs760502262	C>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs796065027	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs796065028	CGGCCTCCGCCCCCGCCCCCGCGCCGCGGCCCCC>-	Pathogenic	Coding sequence variant, frameshift variant
rs796065029	->G	Pathogenic	Coding sequence variant, stop gained
rs878853083	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs886039904	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1057521990	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1064793505	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1064794912	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1064795865	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1064795867	GCCGCGCGCCCCGAGCGCACCTGCCGCCCCCGCACGC>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1085307499	->GC	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1196278287	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1330596542	C>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1356633840	C>G,T	Likely-pathogenic	Missense variant, coding sequence variant
rs1455411788	->A	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1553262429	G>A	Pathogenic	Coding sequence variant, stop gained
rs1553262430	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1553262438	C>G	Likely-pathogenic	Coding sequence variant, stop gained
rs1558119445	->AC	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1571907365	TC>AA	Pathogenic	Coding sequence variant, stop gained
rs1571907430	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1571908452	TGCGGCCTCCC>-	Likely-pathogenic, pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004225	hsa-miR-346	Microarray	16822819
MIRT1019971	hsa-miR-1909	CLIP-seq
MIRT1019972	hsa-miR-298	CLIP-seq
MIRT1019973	hsa-miR-3136-3p	CLIP-seq
MIRT1019974	hsa-miR-3144-5p	CLIP-seq
MIRT1019975	hsa-miR-3155	CLIP-seq
MIRT1019976	hsa-miR-3155b	CLIP-seq
MIRT1019977	hsa-miR-3191	CLIP-seq
MIRT1019978	hsa-miR-3678-3p	CLIP-seq
MIRT1019979	hsa-miR-4267	CLIP-seq
MIRT1019980	hsa-miR-4292	CLIP-seq
MIRT1019981	hsa-miR-4308	CLIP-seq
MIRT1019982	hsa-miR-4421	CLIP-seq
MIRT1019983	hsa-miR-4493	CLIP-seq
MIRT1019984	hsa-miR-4652-5p	CLIP-seq
MIRT1019985	hsa-miR-4667-3p	CLIP-seq
MIRT1019986	hsa-miR-4684-3p	CLIP-seq
MIRT1019987	hsa-miR-484	CLIP-seq
MIRT1019988	hsa-miR-498	CLIP-seq
MIRT1019989	hsa-miR-583	CLIP-seq
MIRT2002024	hsa-miR-4641	CLIP-seq
MIRT1019980	hsa-miR-4292	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
SOX10	Unknown	20695017

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001932	Process	Regulation of protein phosphorylation	IEA
GO:0005243	Function	Gap junction channel activity	IBA	21873635
GO:0005921	Component	Gap junction	IMP	17344063
GO:0005922	Component	Connexin complex	IBA	21873635
GO:0007267	Process	Cell-cell signaling	IBA	21873635
GO:0007420	Process	Brain development	IEA
GO:0009636	Process	Response to toxic substance	IEA
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0010644	Process	Cell communication by electrical coupling	IMP	17344063
GO:0016021	Component	Integral component of membrane	IEA
GO:0033270	Component	Paranode region of axon	IEA
GO:0043204	Component	Perikaryon	IEA
GO:0043209	Component	Myelin sheath	IEA
GO:0055085	Process	Transmembrane transport	IEA
GO:0070447	Process	Positive regulation of oligodendrocyte progenitor proliferation	IEA
GO:1903763	Function	Gap junction channel activity involved in cell communication by electrical coupling	IMP	17344063
GO:1904427	Process	Positive regulation of calcium ion transmembrane transport	IEA
GO:1990769	Component	Proximal neuron projection	IEA
GO:2000134	Process	Negative regulation of G1/S transition of mitotic cell cycle	IEA

Other IDs

• MIM: 608803
• HGNC: 17494
• e!Ensembl: ENSG00000198835

Protein

• UniProt ID: Q5T442
• Protein name: Gap junction gamma-2 protein (Connexin-46.6) (Cx46.6) (Connexin-47) (Cx47) (Gap junction alpha-12 protein)
• Protein function: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a role in myelination in central and peripheral nerv
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00029	Connexin	5 → 291	Connexin	Family

• Sequence:

  MTNMSWSFLTRLLEEIHNHSTFVGKVWLTVLVVFRIVLTAVGGEAIYSDEQAKFTCNTRQ
  PGCDNVCYDAFAPLSHVRFWVFQIVVISTPSVMYLGYAVHRLARASEQERRRALRRRPGP
  RRAPRAHLPPPHAGWPEPADLGEEEPMLGLGEEEEEEETGAAEGAGEEAEEAGAEEACTK
  AVGADGKAAGTPGPTGQHDGRRRIQREGLMRVYVAQLVARAAFEVAFLVGQYLLYGFEVR
  PFFPCSRQPCPHVVDCFVSRPTEKTVFLLVMYVVSCLCLLLNLCEMAHLGLGSAQDAVRG
  RRGPPASAPAPAPRPPPCAFPAAAAGLACPPDYSLVVRAAERARAHDQNLANLALQALRD
  GAAAGDRDRDSSPCVGLPAASRGPPRAGAPASRTGSATSAGTVGEQGRPGTHERPGAKPR
  AGSEKGSASSRDGKTTVWI

• Sequence length: 439

Pathways

Reactome:

Gap junction assembly

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Cerebellar ataxia	Progressive cerebellar ataxia	rs28936415, rs199476133, rs540331226, rs797046006, rs863224069, rs138358708, rs1057519429, rs750959420, rs1568440440, rs1597846084, rs759460806, rs761486324, rs1240335250, rs1596489887
Developmental delay	Global developmental delay, Gross motor development delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Hearing loss	Sensorineural Hearing Loss (disorder)	rs267607135, rs267606855, rs779841884, rs267606854, rs28942097, rs121908073, rs121908076, rs74315289, rs121908144, rs111033313, rs74315437, rs121908348, rs121908349, rs121908350, rs397515359, rs180177151, rs180177154, rs180177153, rs35689081, rs35887622, rs80338944, rs104894396, rs104894398, rs80338947, rs80338948, rs80338942, rs104894402, rs104894403, rs80338945, rs28931594, rs80338940, rs80338941, rs80356590, rs80338950, rs387906706, rs387906707, rs387906708, rs398122848, rs387907016, rs587776894, rs387907088, rs397515411, rs370965183, rs398122930, rs199897298, rs111033187, rs111033448, rs199606180, rs111033284, rs397516413, rs111033305, rs111033220, rs111033256, rs111033297, rs111033253, rs104894408, rs111033295, rs397516874, rs76434661, rs111033335, rs397517323, rs111033247, rs367928692, rs374793617, rs143939430, rs397515605, rs80338939, rs200656442, rs779748859, rs587781261, rs587781262, rs143343083, rs200147906, rs730880338, rs797044491, rs146281367, rs756484720, rs869025593, rs201306709, rs540895576, rs777777359, rs879255246, rs1554358720, rs142498437, rs377145777, rs1057517519, rs779077039, rs952741388, rs1060499797, rs764139009, rs1060499590, rs1064794012, rs1064797115, rs756790858, rs775633137, rs1554952443, rs1554952193, rs782063761, rs1199012623, rs756147087, rs1555648043, rs1555661490, rs1553196233, rs781546107, rs111033190, rs775428246, rs782539587, rs537227442, rs148695069, rs1554835827, rs953422571, rs1554834186, rs1554834161, rs1554835103, rs1554577339, rs1554577402, rs768471577, rs782279338, rs781951909, rs998045226, rs375759781, rs755804651, rs1557458426, rs767797828, rs538027448, rs1559366084, rs367688416, rs1558480402, rs1558490542, rs1559870857, rs1560690591, rs1561299289, rs1562817224, rs1562817529, rs1562822565, rs1562835391, rs1564113368, rs1564554255, rs773851192, rs1564555240, rs761261855, rs1564805114, rs1565522273, rs1565127413, rs781790246, rs1565430886, rs1565469959, rs746667217, rs1565819402, rs1565855932, rs150529554, rs1567939793, rs201866631, rs754472294, rs1559372512, rs1558464965, rs1558488902, rs775062249, rs1226171550, rs1561590396, rs765574676, rs762876554, rs757327146, rs1564949059, rs1565519673, rs368050948, rs1565541888, rs781989117, rs1565402473, rs750358148, rs1386887007, rs1209665716, rs1567641234, rs1237955948, rs1569042782, rs752672077, rs146689036, rs1560070780, rs149712664, rs1564556995, rs762226905, rs773573968, rs1568528171, rs1198256157, rs377267777, rs370564476, rs1577876794, rs747787770, rs759432278, rs1043716893, rs1581138934, rs2033773650, rs1421964916, rs771766431, rs780917129, rs1895773215, rs1895769400, rs761543680, rs1565920060
Leukodystrophy	Leukodystrophy, Leukodystrophy, Hypomyelinating, 2	rs74315475, rs72466451, rs267608671, rs181087667, rs267608682, rs267608674, rs587778271, rs148932047, rs886037931, rs368905417, rs768180196, rs1558211070, rs1558209947, rs1558210191, rs1280845604, rs1382083552, rs1576101665, rs1576080546, rs1576074651, rs1367958450, rs932183417	24374284, 18571143, 22669416, 24357685, 15192806, 19056803, 18094336, 25655951
Leukoencephalopathy	Leukoencephalopathy	rs34757931
Lymphatic malformation	LYMPHATIC MALFORMATION 3	rs267606847, rs267606846, rs587777566, rs587777567, rs786205669, rs869025596, rs869025597, rs869025598, rs869025599, rs869025600, rs869025601, rs1057519263, rs1057519264, rs587776992, rs934897228, rs1569227576, rs1569133268, rs1569226110, rs1569141899, rs1569124017, rs1562967463, rs1567659736, rs1166021430, rs1584651110, rs1574226259	25655951, 18094336, 20537300, 19056803
Myopia	Myopia	rs387907109, rs146936371, rs587776903, rs786205127, rs398122836, rs199624584, rs587777625, rs786205216, rs758872875, rs764211125, rs1135402746, rs765658563, rs1555941129, rs1555941116, rs199923805, rs782555528, rs1554862601, rs1586620121, rs1387950081, rs2051026773, rs1422332023
Optic atrophy	Optic Atrophy	rs121434508, rs267607017, rs80356524, rs80356525, rs879255560, rs104893753, rs80356529, rs397515360, rs104893620, rs199476104, rs199476112, rs199476118, rs398124298, rs770066665, rs398124299, rs61750185, rs672601379, rs727504060, rs786204830, rs794727804, rs199946797, rs863224127, rs863224131, rs863224134, rs863224906, rs372054380, rs886037828, rs764791523, rs145639028, rs1057519312, rs1064794257, rs1064794656, rs1064797303, rs774265764, rs760337383, rs1553784985, rs72653786, rs1555229948, rs1555119216, rs761743852, rs1553785338, rs1020764190, rs782581701, rs1560408865, rs761460379, rs773022324, rs782740998, rs1560327427, rs80356528, rs1734162973, rs1716524583, rs1057368575
Pelizaeus-merzbacher disease	Pelizaeus-Merzbacher-like disease due to GJC2 mutation	rs132630278, rs132630279, rs11543022, rs132630280, rs132630281, rs132630282, rs132630284, rs132630285, rs132630286, rs132630288, rs132630289, rs132630291, rs132630292, rs132630293, rs1569428537, rs1569427707, rs132630296, rs398123467, rs797045064, rs886044450, rs1060499653, rs1060500909, rs1556267215, rs1556273167, rs1556269487, rs1556267388, rs864622194, rs1556267123, rs1556270312, rs1569427311, rs1569427275, rs1455411788, rs1602373055, rs1602382829, rs1602384238, rs1602385663, rs1602383261, rs1602383268
Scoliosis	Scoliosis, unspecified	rs1057518828, rs147296805, rs758163506, rs1555613564, rs1596852902, rs1596853067, rs1596853085
Spastic paraplegia	Spastic Paraplegia, SPASTIC PARAPLEGIA 44, AUTOSOMAL RECESSIVE (disorder), Autosomal recessive spastic paraplegia type 44	rs118204049, rs121918262, rs104894490, rs119476046, rs281865117, rs281865118, rs137853017, rs72554620, rs121908610, rs121908611, rs121908613, rs116171274, rs121434442, rs121434443, rs137852520, rs137852521, rs137852524, rs137852525, rs879253716, rs387906970, rs587776888, rs759947457, rs587776891, rs753426920, rs387907057, rs397514478, rs387907285, rs387907287, rs387907288, rs281865120, rs397514513, rs141431913, rs312262755, rs398123013, rs398123014, rs398122382, rs745744124, rs483352924, rs483352925, rs587777222, rs587779388, rs587783179, rs587783772, rs587784383, rs587784384, rs730882249, rs762947018, rs786204628, rs141315518, rs786204416, rs786204750, rs770866403, rs775059063, rs797044787, rs794729214, rs794729215, rs797045050, rs370828455, rs146262009, rs797045244, rs780247476, rs185246578, rs766773277, rs863224494, rs752669339, rs869320690, rs200737038, rs869312914, rs752283089, rs751713917, rs756205995, rs875989787, rs875989845, rs375817528, rs200440467, rs876661295, rs794727501, rs770285398, rs878854745, rs878854975, rs878855013, rs878855011, rs878855083, rs878853979, rs879255397, rs879255396, rs886039410, rs886039409, rs886039407, rs886039408, rs886039405, rs886039406, rs752598529, rs752059006, rs202199411, rs886041949, rs886041127, rs886042238, rs1057517123, rs747868017, rs1057517294, rs565203731, rs753205260, rs1057517002, rs779338945, rs755186798, rs1057517250, rs1057517060, rs753012964, rs758572409, rs1057516959, rs1057516438, rs145766983, rs1057516689, rs1057516932, rs1057516635, rs1057517366, rs759166250, rs1057517138, rs761089024, rs1057517297, rs1057517311, rs1057516779, rs1057517039, rs1057517285, rs1057516365, rs1057516625, rs1057516987, rs1057516837, rs1057518016, rs1057518880, rs1057518697, rs1057519289, rs1057519290, rs1057519291, rs1057519292, rs1057519293, rs1057521784, rs1060499756, rs1060499771, rs1060502224, rs1060502523, rs371019314, rs1060503431, rs774906736, rs372350326, rs776976178, rs370837940, rs1064793162, rs1064793920, rs1555177629, rs1555394376, rs377445018, rs767024102, rs768176054, rs1557090943, rs1557090161, rs1555178616, rs1555251539, rs754439135, rs1321353475, rs1555186937, rs767871841, rs867249938, rs1440541889, rs1555456727, rs1268722908, rs1557092247, rs1557092248, rs765632065, rs773246271, rs1554380391, rs1554517327, rs200268523, rs1156566314, rs1160357920, rs773182375, rs768366199, rs774809466, rs1555542889, rs915291720, rs1021034246, rs769676029, rs746979262, rs1033093801, rs955142329, rs760559263, rs1557091773, rs1372213267, rs1557091678, rs1402429085, rs1555179091, rs1555179087, rs374128662, rs142209254, rs1553259463, rs1555254256, rs755820725, rs1335804396, rs568176223, rs1555979596, rs780030221, rs1553314978, rs923921184, rs1556840029, rs374894037, rs1553262438, rs1555249362, rs950356390, rs1557091278, rs1557090220, rs1259615333, rs1555249276, rs1555249425, rs1555249479, rs1555249555, rs1555250949, rs1555252349, rs1167474602, rs1175545518, rs1555249648, rs1555249878, rs1400601705, rs1555252086, rs745907077, rs1555249371, rs1555249904, rs1555393393, rs1028098148, rs766711286, rs767164213, rs1470672632, rs1555252184, rs1224762841, rs769329153, rs1555254734, rs1555397331, rs941230062, rs545219731, rs200832994, rs1555250255, rs1240368715, rs1555393338, rs1049504575, rs1485209013, rs868672014, rs1214483973, rs558285072, rs1555398241, rs1186788102, rs981804211, rs935301743, rs1555251822, rs1555255676, rs369459721, rs772400670, rs1558119445, rs759033144, rs1565705251, rs1566055368, rs1566058677, rs1006060877, rs1448182827, rs1569544908, rs754944359, rs754944429, rs1569544723, rs1569285562, rs367916692, rs1566893090, rs1177577061, rs1566881181, rs1569280986, rs1590847310, rs746220436, rs1569281085, rs529495094, rs1563920268, rs1563920252, rs1563920172, rs1563919973, rs1563920000, rs1563920132, rs751568153, rs1569274606, rs1455411788, rs1571908452, rs768640920, rs1578729121, rs1585896928, rs1585808059, rs1588001500, rs1011987148, rs1594915468, rs1594925773, rs1361370524, rs1593121507, rs1365858851, rs1593125341, rs1181477970, rs1593129673, rs1593133395, rs1593133714, rs1593144167, rs1593144544, rs1593144887, rs767435985, rs1593147785, rs994374354, rs1593157923, rs1594900921, rs1594906944, rs1594910045, rs1594913346, rs1594930532, rs1594938339, rs140354725, rs1418885000, rs1603275195, rs1603276234, rs1574077569, rs1603275315, rs1587878722, rs1587879449, rs1593133607, rs770490672, rs1602099961, rs778722037, rs756830713, rs1593121484, rs763869212, rs1594912625, rs1597556143, rs778113360, rs377278120, rs933233143, rs1572337800, rs1573072864, rs1593125290, rs1593126754, rs1593123432, rs1571563769, rs1584514057, rs772704931, rs1587878961, rs1802811311, rs1052410160, rs1298132281, rs748480664, rs139015012, rs1340636078, rs927804920, rs1883405453, rs1883566609, rs1868403104, rs1868480299, rs1868481514, rs1868567420, rs1868626730, rs1868628768, rs1868872666, rs1869006331, rs769212398, rs757179309, rs2039098098, rs2039228359, rs774867891, rs2039613696, rs2039616151, rs2039786680, rs2039997721, rs748149642, rs2040215878, rs760484081, rs1204169977, rs367665974, rs201311640, rs1034820850, rs1930458591, rs1882179247, rs2039758874, rs1885117995, rs1805435464	15192806, 18094336, 20513814, 19056803, 18094336, 25655951

Unknown
Disease name	Disease term	dbSNP ID	References
Cerebral atrophy	Cerebral atrophy
Choreoathetosis	Choreoathetosis
Congenital epicanthus	Congenital Epicanthus
Dysarthria	Dysarthria
Dysmorphic features	Dysmorphic features		20537300, 21266381, 19056803, 22610664, 15192806, 24374284, 23621851
Erysipelas	Erysipelas
Facial paralysis	Facial paralysis
Hemangiosarcoma	Hemangiosarcoma	rs199469669
Hyperkeratosis	Hyperkeratosis
Hypoplasia of corpus callosum	Hypoplasia of corpus callosum
Impaired cognition	Impaired cognition
Milroy disease	Milroy Disease		20537300, 21266381
Motor delay	Clumsiness - motor delay
Movement disorders	Movement Disorders		23621851, 24374284, 22610664, 20537300, 15192806, 19056803, 21266381
Pendular nystagmus	Pendular Nystagmus
Rotary nystagmus	Rotary Nystagmus
Skin neoplasms	Skin Neoplasms
Ataxia, spastic with optic atrophy and mental retardation	ATAXIA, SPASTIC, CHILDHOOD-ONSET, AUTOSOMAL RECESSIVE, WITH OPTIC ATROPHY AND MENTAL RETARDATION
Specific learning disorder	Specific learning disability	rs1057519497
Strabismus	Strabismus
Testicular hydrocele	Testicular Hydrocele
Vulval varices	Varicosity