Table 3: Comprehensive list of human spina bifida genes.

Genes (40 genes) Population and sample size (in brackets) of spina bifida cases References
Studies showed association with genes related NTDs or risk factor for spina bifidaStudies showed no association with genes related NTDs

One carbon metabolism (including homocysteine remethylation) (8 genes)
ALDH1L1Dutch (180 patients)[55]
BHMTMixed USA (259 cases)Mixed USA (252 cases), Dutch (180 patients)[5557]
CHKAMixed USA (103 cases)[58]
MTRRMixed USA (259 cases), mixed UK (229 patients), Dutch (109 cases)Irish (575 mixed families), Dutch (109 cases; 180 patients)[55, 56, 5961]
NOS3Mixed USA (301 families), Dutch (109 cases)Mixed USA (259 cases), Dutch (180 patients)[55, 56, 62, 63]
PYCT1AMixed USA (103 cases)[58]
SARDHDutch (180 patients)[55]
TRDMT1Dutch (180 cases)[55]

NTDs in mouse mutant (7 genes)
BRCA1Mixed USA (268 patients and parents)[64]
CFL1Mixed USA (246 cases)[65]
PAX3USA (74 cases)[66]
PDGFRADutch (88 cases and 56 mothers)Mixed USA (407 triads)[67, 68]
TXN2Mixed USA (48 cases)[69]
ZIC2Dutch (117 mixed patients)[70]
ZIC3Dutch (117 mixed patients)[70]

Folate metabolism (5 genes)
CBSMixed USA (259 cases)Dutch (180 patients)[55, 56]
DHFRIrish (283 cases), mixed USA (61 cases, multiaffected families)Mixed USA (259 cases), mixed UK (229 patients), Dutch (180 patients; 109 patients)[55, 56, 7173]
MTHFD1Irish (509 mixed cases), mixed USA (259 mixed cases), Italian (142 cases), Irish (176 mixed cases)Mixed UK (229 patients), Dutch (103 cases), Dutch (180 patients)[55, 56, 59, 62, 71, 7476]
MTHFRIrish (451 cases), mixed USA (259 cases), mixed UK (229 patients), Italian (15 cases)Dutch (180 patients), Mexican (Yucatan) (97 cases), Italian (15 cases)[55, 56, 59, 60, 77, 78]
TYMSNon-Hispanic white USA (264 cases), mixed USA (259 cases)Dutch (180 patients)[55, 56, 79]

Glucose metabolism (4 genes)
GLUT1Mixed USA (507 cases)[80]
HK1Mixed USA (507 cases)[80]
LEPMixed USA (507 cases)[80]
LEPRMixed USA (507 cases)[80]

DNA repair and DNA methylation (3 genes)
APE1Mixed USA (380 patients)[81]
XPDMixed USA (380 patients)[81]
SOX18Belgium (83 patients) (Rochtus et al., 2016)

Folate transport (2 genes)
CUBNDutch (179 patients)[55]
SLCA19A1, RFC-1Dutch (180 patients)Mixed USA (259 cases), mixed UK (229 patients)[55, 56, 59]

PCP genes (4 gene)
VANGL1Italian and mixed USA (658 patients), Italian and French (102 patients)Mixed UK and USA (24 patients)[44, 82, 83]
CELSR1California (192 patients)[84]
SCRIBCalifornia (192 patients)[85]
DVL1Han Chinese cohort (20 cases)[86]

Retinol metabolism (1 gene)
ALDH1A2Mixed USA (318 families)[87]

Axial development in mouse (1 gene)
T (brachyury)Mixed USA (316 cases)[88]

Methylation reactions (1 gene)
PCMT1Mixed USA (152 cases)Dutch (180 patients)[55, 89]

Oxidative stress (2 genes)
SOD1Mixed USA (610 trios or duos)[90]
SOD2Mixed USA (610 trios or duos)[90]

Intermediate filament protein (1 gene)
LMNB1Mixed UK, USA, and Swedish (233 patients)[91]

Cell adhesion molecules (1 gene)
NCAM1USA (204 patients)[92]

A total of 40 genes reported showing association/risk factor for spina bifida as reviewed in Greene et al. [93].