Table S5. Validation of false positives in the Organ subontology.

Gene	HPO term	PubMed ID	Evidence
DKC1	Postnatal growth retardation	PMID: 10583221	“Hoyeraal-Hreidarsson (HH) syndrome is a multisystem disorder affecting boys characterized by aplastic anaemia (AA), immunodeficiency, microcephaly, cerebellarhypoplasia and growth retardation…We therefore analysed the DKC1 gene in two HH families. In one family a nucleotide change at position 361(A–>G) in exon 5 was found in both affected brothers; in the other family a nucleotide change at position 146(C–>T) in exon 3 was found in the affected boys…”
PEX13	Neonatal hypotonia	PMID:12897163 (mouse)	“…In the studies reported here, we crossed these mice with transgenic mice that express Cre recombinase in all cells to generate progeny with ubiquitous disruption of Pex13. The mutant pups exhibited many of the clinical features of Zellweger syndrome patients, including intrauterine growth retardation, severe hypotonia, failure to feed, and neonatal death…”
PEX13	Retinal dystrophy	PMID:10441568, PMID: 10332040	“…The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment…” (UniProt entry for PEX13)
RPE65	Retinal dystrophy	PMID: 23878505	“…These results strongly suggest that causal mutations in RPE65 are responsible for retinal dystrophy in the affected individuals of these consanguineous Pakistani families…”
BEST1	Retinitis pigmentosa	PMID: 19853238	“…Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa…”
PRPF6	Retinitis pigmentosa	PMID: 21549338	“…A missense mutation in PRPF6 causes impairment of pre-mRNA splicing and autosomal-dominant retinitis pigmentosa…”
SNRNP200	Retinitis pigmentosa	PMID: 19878916	“…Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs…”
ORC1	Emphysema	PMID: 22333897	“…Four individuals were deceased: two siblings with mutations in ORC1, of which one passed away at the age of 3 months with a severe cortical dysplasia, pachygyria and ventricular enlargement, cranial suture stenosis, congenital emphysema of the lung, and absence of the pancreatic tail, in addition to the classical triad of MGS (microtia, patellar anomalies, and short stature)…”
CUL7	Hip dysplasia	PMID: 21396581	“A predisposing factor in hip dysplasia etiology is ligamentous laxity, presented in more than half of the patients with 3M syndrome described in the literature…3M syndrome is an autosomal recessive disorder. In 2005, using an homozygosity mapping strategy, we have mapped the disease locus gene on chromosome 6p21.1 and identified mutations in Cullin 7 ( CUL7, KIAA0076) gene…While CUL7 appears to be the major gene responsible for 3M syndrome accounting for 70% of our cases,…”
ACTB	Postnatal microcephaly	PMID: 22366783	“…Riviere et al. (2012) reported on 10 children with Baraitser-Winter syndrome and mutations in the ACTB gene. Six of the 10 had short stature; 6 of 9 evaluated had postnatal microcephaly;…” (OMIM entry for ACTB)
ACTB	Progressive hearing impairment	PMID:16685646 (mouse)	“…However, aging mice with β- actin or γ-actin deficient hair cells develop different patterns of progressive hearing loss and distinct pathogenic changes in stereocilia morphology, despite colocalization of the actin isoforms…”
MSH2	Gastrointestinal carcinoma	PMID: 8252616	“… hMSH2 maps to human chromosome 2p22-21 near a locus implicated in hereditary nonpolyposis colon cancer (HNPCC)…These data and reports indicating that S.cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene…”
MSH2	Malignant gastrointestinal tract tumors	PMID: 8252616	“… hMSH2 maps to human chromosome 2p22-21 near a locus implicated in hereditary nonpolyposis colon cancer (HNPCC)…These data and reports indicating that S.cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene…”
MSH2	Hereditary nonpolyposis colorectal carcinoma	PMID: 8252616	“… hMSH2 maps to human chromosome 2p22-21 near a locus implicated in hereditary nonpolyposis colon cancer (HNPCC)…These data and reports indicating that S.cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene…”

The columns “HPO term”, “PubMed ID” and “Evidence” provides the false positive prediction made by PHENOStruct for the given gene, PubMed ID of the literature that contains evidence which actually suggests that the prediction should be considered true and the excerpt from that literature which contains the evidence, respectively. We used the 25 false positive predictions for the 17 proteins that had the highest individual protein-centric precision and found evidence for 14 predictions. Two of the evidence comes from studies involving mice (indicated within parentheses with the PubMed ID)