Table 2

 Confirmed and refuted candidate disease gene predictions

Disease subtypeCandidate genesBased on interaction with*Original disease subtypeStatusComments
*These are the known disease genes, associated with other disease subtypes, which have physical protein–protein interactions with the candidate disease genes.
†Square brackets contain OMIM numbers for both diseases and genes.
A prediction is considered confirmed if it is known in published reports to be causative for the relevant disease, and considered refuted if a different gene in the same locus is known to be causative for that disease. It is important to note that a “refuted” candidate gene may not have been screened and excluded, and may thus still be a valid candidate.
Branchiootic syndrome 3 [608389]SIX1 (sine oculis homeobox homolog 1) [601205]†EYA1 (eyes absent homolog 1) [601653]Branchiootic syndrome 1 [602588]ConfirmedConfirmed,24 but not in Morbid Map version used; interaction occurs in fly, worm and HPRD sets
SCID, autosomal recessive, T-negative/B-positive type [600802]JAK3 (Janus kinase 3)LCK (lymphocyte specific protein-tyrosine kinase) [153390]SCID caused by LCK deficiency [153390]ConfirmedRelevant Ensembl gene ID erroneously mapped to INSL3 symbol instead of JAK3, thus JAK3 not mapped to an Ensembl gene ID. All interactions from HPRD
PTPRC (protein-tyrosine phosphatase, receptor type, C) [151460]SCID due to LCK deficiency [151460]
IL2RG (interleukin 2 receptor, γ) [308380]SCID, X linked [300400]
Nephronophthisis 4 [606966]NPHP4 (nephrocystin 4) [607215]NPHP1 (nephrocystin 1) [607100]Nephronophthisis, juvenile [256100]ConfirmedNPHP4 gene symbol not mapped to corresponding Ensembl gene ID in Ensembl database version used. HPRD interaction
Senior-Loken syndrome 4 [606996]Senior-Loken syndrome 1 [266900]
Charcot-Marie-Tooth disease, type 2L [608673]HSPB8 (heat shock 22kDa protein 8) [608014]HSPB1 (heat shock 22 kDa protein 1) [602195]Charcot-Marie-Tooth disease, axonal, type 2F [606595]ConfirmedHSPB8 identified as disease gene in OMIM database, but not in Morbid Map; HPRD interaction
Polycystic kidney disease, infantile severe, with tuberous sclerosis [600273]PKD1 (polycystin 1) [601313]PKD2 (polycystin 2) [173910]Polycystic kidney disease, adult, type II [173910]ConfirmedDisease caused by chromosomal deletion which affects two genes, PKD1 and TSC225; mentioned in OMIM, but not in Morbid Map; HPRD interaction
Pachyonychia congenita, Jadassohn-Lewandowsky type [167200]KRT6A (keratin 6A) [148041]KRT17 (keratin 17) [148069]Pachyonychia congenita, Jackson-Lawler type [167210]ConfirmedEnsembl ID maps to KRT6E, KRT6D, KRT6C and KRT6A; OMIM uses KRT6A name, whereas Ensembl uses KRT6E as primary name, thus mapping to corresponding Ensembl gene ID failed; from human high throughput set
Charcot-Marie-Tooth disease, type 2L [608673]DNCL1 (dynein light chain, LC8-type 1) [601562]DNM2 (dynamin 2) [602378]Charcot-Marie-Tooth disease, dominant intermediate B [606482]RefutedHSPB8 is causative (see above). HSPB8 identified as disease gene in OMIM database, but not in Morbid Map; two HPRD interactions, one yeast
RNF10 (ring finger protein 10) [not in OMIM]GARS (glycyl-tRNA synthetase) [600287]Charcot-Marie-Tooth disease, axonal, type 2D [601472]
MAPKAPK5 (mitogen activated protein kinase-activated protein kinase 5) [606723]HSPB1 (heat shock 22kDa protein 1) [602195]Charcot-Marie-Tooth disease, axonal, type 2F [606595]
Marfan-like connective tissue disorder [154705]FBLN2 (fibulin 2)[135821]FBN1 (fibrillin 1) [134797]Marfan syndrome [154700]RefutedCausative gene is TGFBR2 (TGFβ receptor II) [190182]. FBLN2 was suspected but refuted26; mentioned in OMIM, but not in Morbid Map; HPRD interaction
Retinitis pigmentosa 26 [608380]ENSG00000163510 [not in OMIM]PRPF3 (Pre-MRNA processing factor 3 homolog) [607301]Retinitis pigmentosa 18 [601414]RefutedCausative gene is CRKL (ceramide kinase-like) [608381]; gene name not mapped to Ensembl gene ID in Ensembl; three interactions from yeast set, one from fly set
PRPF8 (Pre-MRNA processing factor 8 homolog) [607300]Retinitis pigmentosa 13 [600059]
PRPF31 (Pre-MRNA processing factor 31 homolog) [606419]Retinitis pigmentosa 11 [600138]
HECW2 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) [not in OMIM]PRPF3 (Pre-MRNA processing factor 3 homolog) [607301]Retinitis pigmentosa 18 [601414]
Retinitis pigmentosa 10 [180105]LUC7L2 (LUC7-like 2) [not in OMIM]PRPF3 (Pre-MRNA processing factor 3 homolog) [607301]Retinitis pigmentosa 18 [601414]RefutedCausative gene is IMPDH1 (IMP dehydrogenase 1) [146690]; Morbid Map version used contains two entries for this subtype, one with and one without associated gene; two from yeast set, one from fly set
PRPF31 (Pre-MRNA processing factor 31 homolog) [606419]Retinitis pigmentosa 11 [600138]
METTL2 (methyltransferase like 2A) [607846]CRX (cone-rod homeobox) [602225]Retinitis pigmentosa, late onset dominant [268000]
Spastic paraplegia 17 [270685]SF3B2 (splicing factor 3b, subunit 2) [605591]HSPD1 (heat shock 60kDa protein 1) [118190]Spastic paraplegia 13 [605280]RefutedKnown gene is BSCL2 (seipin) [606158]; mentioned in OMIM, but not listed in Morbid Map; both from HPRD set, KLC2 also from fly and worm sets
KLC2 (kinesin light chain 2) [601334]KIF5A (kinesin family member 5A) [602821]Spastic paraplegia 10 [604187]
Dyskeratosis congenita, autosomal dominant [127550]EIF4G1 (eukaryotic translation initiation factor 4-γ 1) [600495]DKC1 (dyskerin 1) [300126]Dyskeratosis congenital 1 [305000]RefutedCausative gene is TERC (telomerase RNA component) [602322]; gene symbol not mapped to Ensembl gene ID in Ensembl database version used; three from fly set (EIF4G1, EIF4A2, KPNA1) one from yeast (CPA3)
EIF4A2 (eukaryotic translation initiation factor 4A, isoform 2) [601102]
KPNA1 (karyopherin α 1) [600686]
CPA3 (carboxypeptidase A3, mast cell) [114851]